document_title: Royal Rumble

question_text: who has won the royal rumble the most

question_tokens: who has won the royal rumble the most

text: Royal Rumble

text: History

text: Event

text: The Royal Rumble is a pay-per-view consisting of the Royal Rumble match, title matches, and various other matches. The first Royal Rumble took place on January 24, 1988, and was broadcast live on the USA Network.[4] The following year, the event started to be broadcast on pay-per-view[5] and thus became one of WWE's "big four" pay-per-views, along with WrestleMania, Survivor Series, and SummerSlam.[6]

text: The Royal Rumble match is usually located at the top of the card, though there have been exceptions such as the 1988, 1996, 1997, 1998, 2006, and 2013 events.[7] Due to the Rumble match taking up a large amount of time (most Rumble matches last roughly one hour), the Rumble event tends to have a smaller card than most other pay-per-view events, which routinely have six to eight matches per card. The 2008 Royal Rumble was the first WWE pay-per-view to be available in high-definition.[8]

text: Match

text: The Royal Rumble is based on the classic Battle Royal match, in which a number of wrestlers (usually 30) aim at eliminating their competitors by tossing them over the top rope, with both feet touching the floor.[1][2][9] The winner of the event is the last wrestler remaining after all others have been eliminated.[1][10] According to Hornswoggle, who worked for WWE from 2006 until 2016 and participated in two Rumbles, participants may learn their eliminations by knowing the two wrestlers who are eliminated before them and which wrestlers are entering the Royal Rumble in between their elimination.[11]

text: The Royal Rumble differs from the classical Battle Royal as the contestants do not enter the ring at the same time but instead are assigned entry numbers, usually via a lottery, although desirable spots are occasionally assigned by other means, the most common being winning a match. This lottery is usually staged right before the event begins.[1] The match begins with the two wrestlers who have drawn entry numbers one and two, with the remaining wrestlers entering the ring at regular timed intervals, either 90 seconds or two minutes, according to their entry number.[1] This format is credited to Pat Patterson.[12] To date, only four men who have been one of the starting wrestlers have won the Royal Rumble: Shawn Michaels, Vince McMahon, Chris Benoit and Rey Mysterio. The most common number to win is number 27.

text: The Royal Rumble match commonly involves 30 wrestlers and usually lasts an hour, with the longest match, at the 2011 event, lasting over one hour and nine minutes of a three-hour pay-per-view.[13] However, the first match, contested in 1988, involved only 20 men,[14] and lasted 33 minutes of the two-hour broadcast.[13] The 1998 Royal Rumble nominally had the traditional 30-man field, but only 28 individual wrestlers competed; Mick Foley entered the Royal Rumble match three different times—first as Cactus Jack, then as Mankind, and finally as Dude Love.[15] The 2011 Royal Rumble had a 40-man field,[16] out of whom Alberto Del Rio was victorious.

text: The match has no stipulations or rules other than that elimination must occur by a participant being placed over the top rope and both feet touching the floor. A wrestler who only touches the floor with one foot is not eliminated from the match, a rule which greatly affected the 1995 match, allowing Shawn Michaels to re-enter the ring and win the match.[17] Subsequently, a wrestler who exits the ring without going over the top rope is not eliminated from the contest. For example, during the 1999 match, both Vince McMahon and Steve Austin left the ring, only to return later in the match.[18] In the 1994 match, the last two participants, Bret Hart and Lex Luger, were declared co-winners when it was decided that both of their feet touched the floor at exactly the same time.[19] A similar situation occurred in the 2005 match. However, the match was instead restarted after Batista and John Cena eliminated each other at the same time (as their simultaneous elimination was actually an accident); Batista eliminated Cena afterwards to win the match.[20] Though various referees are charged with observing the match, some eliminations have gone unnoticed to allow the eliminated participants to sneak back into the ring to continue. Steve Austin was able to win in this way during the 1997 match after re-entering following an unacknowledged elimination and eventually tossed Bret Hart, who was the last legal wrestler in the ring, over the top.[21]

text: Although the vast majority of eliminations are caused by active participants, eliminations caused by other means have occurred, and have been ruled legitimate, including self-eliminations (such as Andre the Giant jumping out of the ring after seeing a snake in 1989, Kane eliminating himself in 1999, and Drew Carey eliminating himself in 2001; however, Randy Savage's jump over the top rope in 1992 was not ruled as self-elimination), elimination from previously-eliminated participants (such as The Undertaker eliminating Maven in 2002, Kurt Angle eliminating Shawn Michaels in 2005, Kane eliminating CM Punk in 2014, and The Wyatt Family eliminating Brock Lesnar in 2016), and elimination from non-participants (such as Shane McMahon eliminating Shawn Michaels in 2006 and The Miz eliminating John Cena in 2011). Furthermore, if an injured wrestler is taken away by medical staff, he can return to the match as long as the match is still ongoing (such as Steve Austin in 1999 or Roman Reigns in 2016), but if the match ends without the injured wrestler returning, he is deemed eliminated (such as Scotty 2 Hotty in 2005 or Curtis Axel in 2015).

text: Prize

text: Since 1993, the winner of the Royal Rumble match is traditionally awarded a title match for WWE's top championship at WrestleMania – presently, there are two top championships, the WWE Championship on SmackDown and the WWE Universal Championship on Raw.[22]

text: With the brand extension introduced in mid-2002, the 30 entrants from 2003 to 2006 consisted of 15 wrestlers from both the Raw and SmackDown brands. At first, the winner of the match received a shot at their brand's top champion.[23] Starting in 2004, the Rumble winner had the option of challenging any brand's champion. For instance, Chris Benoit switched brands after winning the 2004 Royal Rumble and won the World Heavyweight Championship.[22] From 2007 to 2010, participants from the ECW brand competed along with the Raw and SmackDown brands, with the ECW World Championship added as an option for the winner to challenge for, although no winners ever did.[24] During ECW's participation, the entries for each brand were not evenly divided.[25] The ECW Championship was deactivated in 2010, and the World Heavyweight Championship was unified into the WWE Championship in 2013, leaving the latter as the only title to challenge for until the brand extension returned in July 2016. The winner of the Royal Rumble match now receives a title opportunity for either SmackDown's WWE Championship or Raw's WWE Universal Championship.

text: WWE's top championship has been booked as on the line during the Royal Rumble match on two occasions. In 1992, the vacant WWF World Heavyweight Championship was contested in the 1992 Royal Rumble match, eventually won by Ric Flair,[26] while in 2016, Roman Reigns was scheduled to defend his WWE World Heavyweight Championship as a participant of that year's Royal Rumble match and was entrant number one. This marked the first time that a reigning champion had to defend his title in the match, which was ultimately won by Triple H, who eliminated Reigns before lastly eliminating Dean Ambrose to win. Reigns would go on to earn a match against Triple H at WrestleMania 32 and won back the title.

text: From 2001 to 2007, the Royal Rumble match winner had gone on to win a World Championship title at WrestleMania.[13] After winning the 2008 match, John Cena became the first winner to use his championship opportunity at an event (No Way Out 2008) other than WrestleMania.[27] He also became the first since The Rock in 2000 to win the Royal Rumble match but fail to win the title in his championship opportunity.

text: The Royal Rumble winner may also choose to put his championship opportunity on the line in a match. This was first done in 1996, when Shawn Michaels risked his WrestleMania XII title shot in a match against Owen Hart at In Your House 6. The second time was in 1999, when Stone Cold Steve Austin offered to forfeit his title opportunity to the Big Boss Man, who won third place in the Rumble (Austin was actually the runner-up in that rumble, but the winner, Vince McMahon himself, had voluntarily given up his title opportunity) if McMahon could beat him in a cage match at St. Valentine's Day Massacre: In Your House, which Austin would go on to win. The third time was in 2002, when Kurt Angle convinced Triple H to put his WrestleMania X8 championship spot on the line at No Way Out, a match which Angle won. However, Triple H would later defeat Angle and regain his WrestleMania championship spot. The fourth time was in 2006, when Randy Orton goaded Rey Mysterio into putting his main event spot at WrestleMania 22 on the line at No Way Out, a match which Orton won. Mysterio was eventually reinserted into the main event at WrestleMania, making it a triple threat match, and went on to win the World Heavyweight Championship. On the February 25, 2013, edition of Raw, John Cena successfully defended his WrestleMania 29 WWE Championship opportunity in a match against CM Punk. On February 22, 2015, at Fastlane, Roman Reigns defended his WrestleMania 31 WWE World Heavyweight Championship opportunity against Daniel Bryan.

text: In 2000, The Rock was declared the victor, as the storyline intended. However, it was later revealed that his feet had actually touched before those of The Big Show. A singles match was held at No Way Out, the event following the Royal Rumble, to determine who received the Wrestlemania title shot against the reigning champion Triple H. Big Show won with the help of Shane McMahon. Rock then defeated Big Show in a rematch in March on Raw with the help of Vince McMahon, which earned him a title shot and converted the match at WrestleMania into a triple-threat that was later made a four-way match when Linda McMahon inserted the recently retired Mick Foley into the match.

text: Non-PPV Royal Rumble matches

text: WWE has booked several Royal Rumble matches outside of the annual Royal Rumble event:

text:
The first Royal Rumble match broadcast outside of its pay-per-view was a Tag Team Royal Rumble on June 15, 1998. Kane and Mankind won the match and earned an opportunity for the WWF Tag Team Championship against The New Age Outlaws.
On January 11, 1999, a "Corporate Royal Rumble" involving members of The Corporation and D-Generation X was held on Raw to determine the 30th entry in the Royal Rumble that year. The match was won by Chyna, who last eliminated Mr. McMahon.
A 15-man Royal Rumble was held during the January 29, 2004, edition of SmackDown to crown a contender for Brock Lesnar's WWE Championship at No Way Out. Eddie Guerrero won the match, last eliminating Kurt Angle.
On January 14, 2008, Mr. McMahon organized a mini-Royal Rumble, involving midget wrestlers. Hornswoggle won the match.
On the January 31, 2011, episode of Raw, a Royal Rumble to crown the contender for The Miz's WWE Championship at Elimination Chamber was held. Jerry Lawler won the match, last eliminating Sheamus.

text: WWE has also booked two Royal Rumble matches which were never televised, both in 1994. The first, a 30-man Royal Rumble on January 17, was won by Owen Hart, last eliminating Fatu. The second, an 18-man Royal Rumble match, took place on May 9 in Osaka, Japan, and was won by The Undertaker, who last eliminated Bam Bam Bigelow.

text: Dates, venues, and winners

text:
List of Royal Rumble dates, venues, and winners

Event
Date
City
Venue
Winner
Entry No.
Ref.
Final match

01 !1
Royal Rumble (1988)
January 24, 1988
Hamilton, Ontario
Copps Coliseum
Duggan, JimJim Duggan
13 !13
[28][29]
The Islanders (Haku and Tama) vs. The Young Stallions (Paul Roma and Jim Powers) in a two out of three falls match

02 !2
Royal Rumble (1989)
January 15, 1989
Houston
The Summit
Studd, Big JohnBig John Studd
27 !27
[30][31]
30-man Royal Rumble match

03 !3
Royal Rumble (1990)
January 21, 1990
Orlando, Florida
Orlando Arena
Hogan, HulkHulk Hogan
25 !25
[32][33]
30-man Royal Rumble match

04 !4
Royal Rumble (1991)
January 19, 1991
Miami
Miami Arena
24 !24
[34][35]
30-man Royal Rumble match

05 !5
Royal Rumble (1992)
January 19, 1992
Albany, New York
Knickerbocker Arena
Flair, RicRic Flair
03 !3
[36][37]
30-man Royal Rumble match for the vacant WWF World Heavyweight Championship

06 !6
Royal Rumble (1993)
January 24, 1993
Sacramento, California
ARCO Arena
Yokozuna
27 !27
[38][39]
30-man Royal Rumble match

07 !7
Royal Rumble (1994)
January 23, 1994
Providence, Rhode Island
Providence Civic Center
Bret Hart
Lex Luger
27 !27
23 !23
[40][41]
30-man Royal Rumble match

08 !8
Royal Rumble (1995)
January 22, 1995
Tampa, Florida
USF Sun Dome
Michaels, ShawnShawn Michaels
01 !1
[42][43]
30-man Royal Rumble match

09 !9
Royal Rumble (1996)
January 21, 1996
Fresno, California
Selland Arena
18 !18
[44][45]
Bret Hart (c) vs. The Undertaker for the WWF World Heavyweight Championship

10 !10
Royal Rumble (1997)
January 19, 1997
San Antonio, Texas
Alamodome
Stone Cold Steve Austin
05 !5
[46][47]
Sycho Sid (c) vs. Shawn Michaels for the WWF World Heavyweight Championship

11 !11
Royal Rumble (1998)
January 18, 1998
San Jose, California
San Jose Arena
24 !24
[48][49][50]
Shawn Michaels (c) vs. The Undertaker in a Casket match for the WWF World Heavyweight Championship

12 !12
Royal Rumble (1999)
January 24, 1999
Anaheim, California
Arrowhead Pond
Mr. McMahon
02 !2
[51][52][53]
30-man Royal Rumble match

13 !13
Royal Rumble (2000)
January 23, 2000
New York City
Madison Square Garden
Rock, TheThe Rock
24 !24
[54][55][56]
30-man Royal Rumble match

14 !14
Royal Rumble (2001)
January 21, 2001
New Orleans, Louisiana
New Orleans Arena
Stone Cold Steve Austin
27 !27
[57][58][59]
30-man Royal Rumble match

15 !15
Royal Rumble (2002)
January 20, 2002
Atlanta
Philips Arena
Triple H
22 !22
[60][61][62]
30-man Royal Rumble match

16 !16
Royal Rumble (2003)
January 19, 2003
Boston
FleetCenter
Lesnar, BrockBrock Lesnar
29 !29
[63][64]
30-man Royal Rumble match

17 !17
Royal Rumble (2004)
January 25, 2004
Philadelphia
Wachovia Center
Chris Benoit
01 !1
[65][66][67]
30-man Royal Rumble match

18 !18
Royal Rumble (2005)
January 30, 2005
Fresno, California
Save Mart Center
Batista
28 !28
[68][69][70]
30-man Royal Rumble match

19 !19
Royal Rumble (2006)
January 29, 2006
Miami, Florida
American Airlines Arena
Mysterio, ReyRey Mysterio
02 !2
[71][72][73]
Kurt Angle (c) vs. Mark Henry for the World Heavyweight Championship

20 !20
Royal Rumble (2007)
January 28, 2007
San Antonio, Texas
AT&T Center
Undertaker, TheThe Undertaker
30 !30
[74][75][76]
30-man Royal Rumble match

21 !21
Royal Rumble (2008)
January 27, 2008
New York City, New York
Madison Square Garden
Cena, JohnJohn Cena
30 !30
[77][78][79]
30-man Royal Rumble match

22 !22
Royal Rumble (2009)
January 25, 2009
Detroit, Michigan
Joe Louis Arena
Orton, RandyRandy Orton
08 !8
[80][81]
30-man Royal Rumble match

23 !23
Royal Rumble (2010)
January 31, 2010
Atlanta, Georgia
Philips Arena
Edge
29
[82][83]
30-man Royal Rumble match

24 !24
Royal Rumble (2011)
January 30, 2011
Boston, Massachusetts
TD Garden
Del Rio, AlbertoAlberto Del Rio
38
[84]
40-man Royal Rumble match

25 !25
Royal Rumble (2012)
January 29, 2012
St. Louis, Missouri
Scottrade Center
Sheamus
22
[85][86][87]
30-man Royal Rumble match

26 !26
Royal Rumble (2013)
January 27, 2013
Phoenix, Arizona
US Airways Center
Cena, JohnJohn Cena
19
[88][89][90]
CM Punk (c) vs. The Rock for the WWE Championship

27 !27
Royal Rumble (2014)
January 26, 2014
Pittsburgh, Pennsylvania
Consol Energy Center
Batista
28
[91][92]
30-man Royal Rumble match

28 !28
Royal Rumble (2015)
January 25, 2015
Philadelphia, Pennsylvania
Wells Fargo Center
Reigns, RomanRoman Reigns
19
[93]
30-man Royal Rumble match

29 !29
Royal Rumble (2016)
January 24, 2016
Orlando, Florida
Amway Center
Triple H
30
[94][95]
30-man Royal Rumble match for the WWE World Heavyweight Championship; reigning champion Roman Reigns defended the title in the match

30 !30
Royal Rumble (2017)
January 29, 2017
San Antonio, Texas
Alamodome
Randy Orton
23
[96]
30-man Royal Rumble match

31 !31
Royal Rumble (2018)
January 28, 2018
Philadelphia, Pennsylvania
Wells Fargo Center
TBD
TBD
[97]
TBD

text: Royal Rumble winner's championship opportunity

text:
Championship
Wins
Losses
Total

WWE Championship
8
7
15

World Heavyweight Championship
5
2
7

Total
13
9
22

text:
Winner
Event
Year
Championship match

01 !1
Yokozuna
WrestleMania IX
1993
Yokozuna defeated Bret Hart for the WWF World Heavyweight Championship.

02 !2
Lex Luger
WrestleMania X
1994
Luger lost to Yokozuna by disqualification for the WWF World Heavyweight Championship.

02 !2
Bret Hart
WrestleMania X
1994
Hart defeated Yokozuna for the WWF World Heavyweight Championship.

03 !3
Shawn Michaels
WrestleMania XI
1995
Michaels lost to Diesel for the WWF World Heavyweight Championship.

04 !4
Shawn Michaels
WrestleMania XII
1996
Michaels successfully defended his title shot against Owen Hart at In Your House 6. Michaels went on to defeat Bret Hart for the WWF World Heavyweight Championship.

05 !5
Stone Cold Steve Austin
WrestleMania 13
1997
Due to Austin re-entering the Rumble match because the officials did not see when he was thrown out of the ring, WWF President Gorilla Monsoon ruled that he would not be receiving the WrestleMania 13 title shot. A match in February was signed to determine who would receive it, but champion Shawn Michaels' forfeiting the title changed those plans. The WrestleMania main event pitted The Undertaker against Sycho Sid.

06 !6
Stone Cold Steve Austin
WrestleMania XIV
1998
Austin defeated Shawn Michaels for the WWF World Heavyweight Championship.

07 !7
Mr. McMahon
WrestleMania XV
1999
The following night on Raw Is War, McMahon renounced his title opportunity to challenge then WWF Champion, The Rock, at WrestleMania. WWF Commissioner Shawn Michaels awarded the title opportunity to the runner-up, Stone Cold Steve Austin, who defeated McMahon in a steel cage match to retain his opportunity and would go on to WrestleMania to defeat The Rock for the WWF Championship.

08 !8
The Rock
WrestleMania 2000
2000
Video footage later showed Rock's feet hit the floor first before runner-up Big Show. After multiple attempts to name a rightful No. 1 contender failed, both The Rock and Big Show were added to the main event along with Mick Foley to challenge the champion Triple H. Triple H was able to successfully defend the WWF Championship in a four corner elimination match.

09 !9
Stone Cold Steve Austin
WrestleMania X-Seven
2001
Austin defeated The Rock in a no disqualification match for the WWF Championship.

10 !10
Triple H
WrestleMania X8
2002
Triple H lost his WrestleMania title shot to Kurt Angle at No Way Out. The following night on Raw, Triple H won his title shot back and would defeat Chris Jericho for the Undisputed WWF Championship.

11 !11
Brock Lesnar
WrestleMania XIX
2003
Lesnar defeated Kurt Angle for the WWE Championship.

12 !12
Chris Benoit
WrestleMania XX
2004
Benoit won the Rumble as a SmackDown! wrestler, but switched to the Raw brand to challenge Triple H for the World Heavyweight Championship. He defeated Triple H and Shawn Michaels in a triple threat match for the World Heavyweight Championship.

13 !13
Batista
WrestleMania 21
2005
Batista defeated Triple H for the World Heavyweight Championship.

14 !14
Rey Mysterio
WrestleMania 22
2006
Mysterio lost his WrestleMania title shot to Randy Orton at No Way Out. SmackDown! general manager Theodore Long later added Mysterio to the World Heavyweight Championship match at WrestleMania, making it a triple threat match. At WrestleMania 22, Mysterio defeated the champion Kurt Angle and Orton in a triple threat match to win the World Heavyweight Championship.

15 !15
The Undertaker
WrestleMania 23
2007
Undertaker defeated Batista for the World Heavyweight Championship.

16 !16
John Cena
No Way Out (2008)
WrestleMania XXIV
2008
Instead of waiting until WrestleMania, Cena used his WWE Championship shot at No Way Out against Randy Orton. Orton remained champion due to being disqualified. A triple threat match for the WWE Championship was held at WrestleMania XXIV, also including Triple H. Orton successfully retained.

17 !17
Randy Orton
WrestleMania XXV
2009
Orton lost to Triple H for the WWE Championship.

18 !18
Edge
WrestleMania XXVI
2010
Edge lost to Chris Jericho for the World Heavyweight Championship.

19 !19
Alberto Del Rio
WrestleMania XXVII
2011
Del Rio lost to Edge for the World Heavyweight Championship.

20 !20
Sheamus
WrestleMania XXVIII
2012
Sheamus defeated Daniel Bryan for the World Heavyweight Championship.

21 !21
John Cena
WrestleMania 29
2013
On the February 25 episode of Raw, Cena successfully defended his title shot against CM Punk. Cena went on to defeat The Rock for the WWE Championship.

22 !22
Batista
WrestleMania XXX
2014
Daniel Bryan defeated Triple H in the opening match, with the winner being inserted into the WWE World Heavyweight Championship match. Bryan defeated the champion Randy Orton and Batista in a triple threat match.

23 !23
Roman Reigns
WrestleMania 31
2015
Reigns successfully defended his title shot at Fastlane against Daniel Bryan. Reigns went on to challenge Brock Lesnar for the WWE World Heavyweight Championship at WrestleMania 31. During the match at WrestleMania, Seth Rollins cashed in his Money in the Bank contract, converting the singles match between Reigns and Lesnar into a triple threat match. Rollins pinned Reigns to win the WWE World Heavyweight Championship.

24 !24
Randy Orton
WrestleMania 33
2017
Orton stated his intent to challenge for SmackDown's WWE Championship. However, after his fellow Wyatt Family member Bray Wyatt won the championship at Elimination Chamber and retained it on the following SmackDown, Orton said he would not face Wyatt for the title at WrestleMania. On the February 28 episode of SmackDown, Orton reverted his decision and turned on Wyatt; the following week, he defeated AJ Styles, who had become the new number one contender for the title, to re-earn his title shot against Wyatt at WrestleMania. At the event, Orton defeated Wyatt to win the championship

text: Note: There was no WrestleMania title opportunity for the winners of the 1992 and 2016 Royal Rumble matches. In 1992, Ric Flair won the Royal Rumble match, which was for the vacant WWF World Heavyweight Championship. In 2016, Triple H won the Royal Rumble match in which Roman Reigns defended the WWE World Heavyweight Championship.

text: Royal Rumble records

text: Most Rumble victories

text:
No
Wrestler
Royal Rumble wins
Year

1
Stone Cold Steve Austin
3
1997, 1998, 2001

2
Hulk Hogan
2
1990, 1991

Shawn Michaels
1995, 1996

Triple H
2002, 2016

Batista
2005, 2014

John Cena
2008, 2013

Randy Orton
2009, 2017

text: Longest time spent in a single Royal Rumble

text: Top 20 individual longest times in a single Royal Rumble match. As of the 2017 Royal Rumble.

text:
No
Wrestler
Time
Year

1
Rey Mysterio
1:02:12
2006[98]

2
Chris Benoit
1:01:31
2004[98]

3
Bob Backlund
1:01:10
1993[98]

4
Triple H
1:00:16
2006

5
Chris Jericho
1:00:13
2017

6
Ric Flair
1:00:02
1992[98]

7
Roman Reigns
59:50
2016

8
Mr. McMahon
56:38
1999

Stone Cold Steve Austin
56:38
1999

10
Kane
53:46
2001

11
Rick Martel
52:17
1991[98]

12
The Rock
51:32
1998

13
Chris Jericho
50:50
2016

14
Triple H
49:58
2009

15
Dolph Ziggler
49:47
2013

16
Rey Mysterio
49:24
2009

17
CM Punk
49:11
2014

18
Seth Rollins
48:31
2014

19
Randy Orton
48:27
2009

20
Triple H
48:04
1996

text: Note: bold indicates the winner of that year's match

text: Longest cumulative time spent in Royal Rumbles

text: Only wrestlers who have spent more than 3 cumulative hours are shown. As of the 2017 Royal Rumble.

text:
No
Wrestler
Time

1
Chris Jericho
4:56:00 [99]

2
Triple H
4:00:02

3
Shawn Michaels
3:42:30[99]

4
Isaac Yankem/Diesel/Kane
3:38:46

5
Rey Mysterio
3:20:01

6
Cody Rhodes/Stardust
3:08:30

text: Shortest time spent in a single Royal Rumble

text: Only wrestlers who spent 10 seconds or less in a single rumble are shown. As of the 2017 Royal Rumble.

text:
No
Wrestler
Time
Year

1
Santino Marella
0:00:01
2009[98]

2
The Warlord
0:00:02
1989[98]

3
Mo
0:00:03
1995[98]

Owen Hart
0:00:03
1995[98]

5
Bushwhacker Luke
0:00:04
1991

Jerry Lawler
0:00:04
1997

Titus O'Neil
0:00:04
2015

8
The Godfather
0:00:05
2013[98]

9
Gillberg
0:00:07
1999

The Miz
0:00:07
2007

Montel Vontavious Porter
0:00:07
2010

12
Adam Rose
0:00:08
2015

13
Tazz
0:00:10
2001

text: Non-eliminated wrestlers

text: Several times, wrestlers were drawn to compete in the match but did not actually compete. Their participation is counted as zero seconds, with the exception of #6 Hornswoggle:

text:
In 1991, "Macho King" Randy Savage was drawn 18th, but no-showed due to leaving the building after costing Ultimate Warrior the WWF Championship against Sgt. Slaughter.
In 1994, Bastion Booger was drawn 25th, but no-showed due to suffering food poisoning before the match.
In 1998, Skull was drawn 22nd, but no-showed due to being attacked by Los Boricuas after being mistaken for Stone Cold Steve Austin.
In 2004, Spike Dudley was drawn 13th, but was attacked on the ramp by Kane
In 2005, Scotty 2 Hotty was drawn 15th, but was attacked on the ramp by Muhammad Hassan.
In 2008, Hornswoggle was drawn 9th and eliminated The Miz, however he wasn't brought into the ring until towards the end of the match by Mark Henry and was saved by Finlay and escorted to the back and never reentered the match.
In 2008, Finlay was drawn 27th, but was disqualified after coming out before his number came up and using his shillelagh to help Hornswoggle.
In 2015, Curtis Axel was drawn 6th, but was attacked on the ramp by Erick Rowan.

tag: ol

text: Most eliminations in a single Royal Rumble

text: Top wrestlers with most eliminations in a single match. Only wrestlers with at least seven eliminations are shown. As of the 2017 Royal Rumble.

text:
No
Wrestler
No. of eliminations
Year

1
Roman Reigns
12
2014[100]

2
Kane
11
2001[98][101]

3
Hulk Hogan
10
1989[98][102]

Stone Cold Steve Austin
10
1997[98][103]

5
Shawn Michaels
8
1995, 1996

Stone Cold Steve Austin
8
1999

7
Hulk Hogan
7
1991

Yokozuna
7
1993

Diesel
7
1994

Stone Cold Steve Austin
7
1998, 2002

Rikishi
7
2000

The Undertaker
7
2002

The Great Khali
7
2007

CM Punk
7
2011

John Cena
7
2011

Braun Strowman
7
2017

text: Total eliminations in cumulative Royal Rumbles

text: Top wrestlers with the most eliminations. Only wrestlers with at least 20 eliminations are shown. As of the 2017 Royal Rumble.[104]

text:
No
Wrestler
No. of eliminations
Rumbles entered

1
Isaac Yankem/Kane
44
19[98][105][106]

2
Shawn Michaels
39
12[107][108]

The Undertaker
39
11

4
The Ringmaster/Stone Cold Steve Austin
36
6[98]

5
Triple H
33
9

6
Big Show
31
12

7
Hulk Hogan
27
4

8
Roman Reigns
26
4

9
John Cena
22
7

10
Randy Orton
20
7

text: Most Rumble appearances

text: Only wrestlers with at least 9 appearances are shown. As of the 2017 Royal Rumble.

text:
No
Wrestler
Rumbles entered
First Rumble
Most recent Rumble

1
Isaac Yankem/Diesel/Kane
19
1996
2016

2
Shawn Michaels
12
1989
2010

Big Show
2000
2017

4
Goldust
11
1997
2016

The Undertaker
1991
2017

6
The Sultan/Fatu/Rikishi
10
1993
2004

Mark Henry
1998
2017

The Miz
2007
2017

Chris Jericho
2000
2017

10
Mabel/Viscera/Big Daddy V
9
1994
2008

Triple H
1996
2016

K-Kwik/R-Truth
2001
2016

Kofi Kingston
2009
2017

Dolph Ziggler
2009
2017

text: Female entrants

text:
No
Diva
Rumbles entered

1
Chyna
2 (1999, 2000)[52][55]

2
Beth Phoenix
1 (2010)[83]

3
Kharma
1 (2012)

text: Non-PPV Royal Rumble matches

text:
List of Royal Rumble dates, venues, and winners

Event
Date
City
Venue
Winner
Ref.
Note

01 !1
House show
January 17, 1994
New York City
Madison Square Garden
Owen Hart
[109]
30-man Royal Rumble

2
House show
May 9, 1994
Osaka, Japan
Castle Hall
The Undertaker
[109]
18-man Royal Rumble

3
Raw
June 15, 1998
San Antonio, Texas
Freeman Coliseum
Kane and Mankind
[109]
10-tag team Royal Rumble

4
Raw
January 11, 1999
Houston
Compaq Center
Chyna
[109]
Corporate Rumble

5
SmackDown
January 29, 2004
Washington, D.C.
MCI Center
Eddie Guerrero
[110]
15-man SmackDown! Royal Rumble

6
Raw
January 14, 2008
Mobile, Alabama
Mobile Civic Center
Hornswoggle
[111]
Mini Royal Rumble; all participants were midget wrestlers

7
Raw
January 31, 2011
Providence, Rhode Island
Dunkin' Donuts Center
Jerry Lawler
[112]
7-man Raw Rumble

text: Video box set

text: In March 2007, WWE released a complete DVD box set titled Royal Rumble: The Complete Anthology, which showcases every Royal Rumble event in its entirety, up to the 2007 Royal Rumble.[113]


document_title: Neuromuscular-blocking drug

question_text: the only depolarizing muscle relaxant in clinical use is

root

text: Neuromuscular-blocking drug

text: Nomenclature[edit]

text: Neuromuscular blocking drugs are often classified into two broad classes:

tag: p

text:
Pachycurares, which are bulky molecules with nondepolarizing activity
Leptocurares, which are thin and flexible molecules that tend to have depolarizing activity.[3]

tag: ul

text: It is also common to classify them based on their chemical structure.

text: Acetylcholine, suxamethonium, and decamethonium

text: Suxamethonium was synthesised by connecting two acetylcholine molecules and has the same number of heavy atoms between methonium heads as decamethonium. Just like acetylcholine, succinylcholine, decamethonium and other polymethylene chains, of the appropriate length and with two methonium, heads have small trimethyl onium heads and flexible links. They all exhibit a depolarizing block.

text: Aminosteroids

text: Pancuronium, vecuronium, rocuronium, rapacuronium, dacuronium, malouètine, duador, dipyrandium, pipecuronium, chandonium (HS-310), HS-342 and other HS- compounds are aminosteroidal agents. They have in common the steroid structural base, which provides a rigid and bulky body. Most of the agents in this category would also be classified as non-depolarizing.

text: Tetrahydroisoquinoline derivatives

text: Compounds based on the tetrahydroisoquinoline moiety such as atracurium, mivacurium, and doxacurium would fall in this category. They have a long and flexible chain between the onium heads, except for the double bond of mivacurium. D-tubocurarine and dimethyltubocurarine are also in this category. Most of the agents in this category would be classified as non-depolarizing.

text: Gallamine and other chemical classes

text: Gallamine is a trisquaternary ether with three ethonium heads attached to a phenyl ring through an ether linkage. Many other different structures have been used for their muscle relaxant effect such as alcuronium (alloferin), anatruxonium, diadonium, fazadinium (AH8165) and tropeinium.

text: Novel NMB agents

text: In recent years much research has been devoted to new types of quaternary ammonium muscle relaxants. These are asymmetrical diester isoquinolinium compounds and bis-benzyltropinium compounds that are bistropinium salts of various diacids. These classes have been developed to create muscle relaxants that are faster and shorter acting. Both the asymmetric structure of diester isoquinolinium compounds and the acyloxylated benzyl groups on the bisbenzyltropiniums destabilizes them and can lead to spontaneous breakdown and therefore possibly a shorter duration of action.[4]

text: Classification[edit]

text: These drugs fall into two groups:

text:
Non-depolarizing blocking agents: These agents constitute the majority of the clinically relevant neuromuscular blockers. They act by competitively blocking the binding of ACh to its receptors, and in some cases, they also directly block the ionotropic activity of the ACh receptors.[5]
Depolarizing blocking agents: These agents act by depolarizing the sarcolemma of the skeletal muscle fiber. This persistent depolarization makes the muscle fiber resistant to further stimulation by ACh.

text: Non-depolarizing blocking agents[edit]

text: A neuromuscular non-depolarizing agent is a form of neuromuscular blocker that does not depolarize the motor end plate.[6]

text: The quaternary ammonium muscle relaxants belong to this class.

text: Below are some more common agents that act as competitive antagonists against acetylcholine at the site of postsynaptic acetylcholine receptors.

text: Tubocurarine, found in curare of the South American plant Pareira, Chondrodendron tomentosum, is the prototypical non-depolarizing neuromuscular blocker. It has a slow onset (>5 min) and a long duration of action (30 mins). Side-effects include hypotension, which is partially explained by its effect of increasing histamine release, a vasodilator,[7] as well as its effect of blocking autonomic ganglia.[8] It is excreted in the urine.

text: This drug needs to block about 70–80% of the ACh receptors for neuromuscular conduction to fail, and hence for effective blockade to occur. At this stage, end-plate potentials (EPPs) can still be detected, but are too small to reach the threshold potential needed for activation of muscle fiber contraction.

text:
Comparison of non-depolarizing neuromuscular blocking agents

Agent
Time to onset
(seconds)
Duration
(minutes)
Side effects
Clinical use
Storage

Rapacuronium (Raplon)

Mivacurium (Mivacron)
90
12–18[9]

hypotension (transiently), by release of histamine[9]

No longer manufactured secondary to marketing, manufacturing, and financial concerns
refrigerated

Atracurium (Tracrium)
90
30 min or less[9]

hypotension, transiently,[9] by release of histamine
Toxic metabolite called laudanosine, greater accumulation in individuals with renal failure

widely[9]
refrigerated

Doxacurium (Nuromax)

long[9]

hypotension, transiently,[9] by release of histamine
Toxic metabolite called laudanosine, greater accumulation in individuals with renal failure

Cisatracurium (Nimbex)
90
60–80
does not cause release of histamine

refrigerated

Vecuronium (Norcuron)
60
30–40[9]
Few,[9] may cause prolonged paralysis[9] and promote muscarinic block
widely[9]
non-refrigerated

Rocuronium (Zemuron)
75
45–70[citation needed]
may promote muscarinic block

non-refrigerated

Pancuronium (Pavulon)
90
180 or more[citation needed]

tachycardia (slight)[9]

(no hypotension)[9]

widely[9]
non-refrigerated

Tubocurarine (Jexin)
300 or more[9]
60–120[9]

hypotension (by ganglion-block and histamine release)[9]
Bronchoconstriction (by histamine release)[9]

rarely[9]

gallamine (Flaxedil)
300 or more[9]
60–120[9]

tachycardia

Pipecuronium
90
180 or more[citation needed]

tachycardia (slight)[9]

(no hypotension)[9]

non-refrigerated

tag: table

text: Depolarizing blocking agents[edit]

text: A depolarizing neuromuscular blocking agent is a form of neuromuscular blocker that depolarizes the motor end plate.[10]

text: An example is succinylcholine.

text: Depolarizing blocking agents work by depolarizing the plasma membrane of the muscle fiber, similar to acetylcholine. However, these agents are more resistant to degradation by acetylcholinesterase, the enzyme responsible for degrading acetylcholine, and can thus more persistently depolarize the muscle fibers. This differs from acetylcholine, which is rapidly degraded and only transiently depolarizes the muscle.

text: There are two phases to the depolarizing block. During phase I (depolarizing phase), they cause muscular fasciculations (muscle twitches) while they are depolarizing the muscle fibers. Eventually, after sufficient depolarization has occurred, phase II (desensitizing phase) sets in and the muscle is no longer responsive to acetylcholine released by the motoneurons. At this point, full neuromuscular block has been achieved.

text: The prototypical depolarizing blocking drug is succinylcholine (suxamethonium). It is the only such drug used clinically. It has a rapid onset (30 seconds) but very short duration of action (5–10 minutes) because of hydrolysis by various cholinesterases (such as butyrylcholinesterase in the blood). Succinylcholine was originally known as diacetylcholine because structurally it is composed of two acetylcholine molecules joined with a methyl group. Decamethonium is sometimes, but rarely, used in clinical practice.

text: Comparison of drugs[edit]

text: The main difference is in the reversal of these two types of neuromuscular-blocking drugs.

text:
Non-depolarizing blockers are reversed by acetylcholinesterase inhibitor drugs since non-depolarizing blockers are competitive antagonists at the ACh receptor so can be reversed by increases in ACh.
The depolarizing blockers already have ACh-like actions, so these agents have prolonged effect under the influence of acetylcholinesterase inhibitors. Administration of depolarizing blockers initially produces fasciculations (a sudden twitch just before paralysis occurs). This is due to depolarization of the muscle. Also, post-operative pain is associated with depolarizing blockers.

text: The tetanic fade is the failure of muscles to maintain a fused tetany at sufficiently high frequencies of electrical stimulation.

text:
Non-depolarizing blockers have this effect on patients, probably by an effect on presynaptic receptors.[11]
Depolarizing blockers do not cause the tetanic fade. However, a clinically similar manifestation called Phase II block occurs with repeated doses of suxamethonium.

text: This discrepancy is diagnostically useful in case of intoxication of an unknown neuromuscular-blocking drug.[11]

text: Mechanism of action[edit]

text: Quaternary muscle relaxants bind to the nicotinic acetylcholine receptor and inhibit or interfere with the binding and effect of ACh to the receptor. Each ACh-receptor has two receptive sites and activation of the receptor requires binding to both of them. Each receptor site is located at one of the two α-subunits of the receptor. Each receptive site has two subsites, an anionic site that binds to the cationic ammonium head and a site that binds to the blocking agent by donating a hydrogen bond.[3]

text: Non-depolarizing agents A decrease in binding of acetylcholine leads to a decrease in its effect and neuron transmission to the muscle is less likely to occur. It is generally accepted that non-depolarizing agents block by acting as reversible competitive inhibitors. That is, they bind to the receptor as antagonists and that leaves fewer receptors available for acetylcholine to bind.[3][12]

text: Depolarizing agents Depolarizing agents produce their block by binding to and activating the ACh receptor, at first causing muscle contraction, then paralysis. They bind to the receptor and cause depolarization by opening channels just like acetylcholine does. This causes repetitive excitation that lasts longer than a normal acetylcholine excitation and is most likely explained by the resistance of depolarizing agents to the enzyme acetylcholinesterase. The constant depolarization and triggering of the receptors keeps the endplate resistant to activation by acetylcholine. Therefore, a normal neuron transmission to muscle cannot cause contraction of the muscle because the endplate is depolarized and thereby the muscle paralysed.[3][12]

text: Binding to the nicotinic receptor Shorter molecules like acetylcholine need two molecules to activate the receptor, one at each receptive site. Decamethonium congeners, which prefer straight line conformations (their lowest energy state), usually span the two receptive sites with one molecule (binding inter-site). Longer congeners must bend when fitting receptive sites.

text: The greater energy a molecule needs to bend and fit usually results in lower potency.[13]

text: Structural and conformational action relationship[edit]

text: Conformational study on neuromuscular blocking drugs is relatively new and developing. Traditional SAR studies do not specify environmental factors on molecules. Computer-based conformational searches assume that the molecules are in vacuo, which is not the case in vivo. Solvation models take into account the effect of a solvent on the conformation of the molecule. However, no system of solvation can mimic the effect of the complex fluid composition of the body.[14]

text: The division of muscle relaxants to rigid and non-rigid is at most qualitative. The energy required for conformational changes may give a more precise and quantitative picture. Energy required for reducing onium head distance in the longer muscle relaxant chains may quantify their ability to bend and fit its receptive sites.[13] Using computers it is possible to calculate the lowest energy state conformer and thus most populated and best representing the molecule. This state is referred to as the global minimum. The global minimum for some simple molecules can be discovered quite easily with certainty. Such as for decamethonium the straight line conformer is clearly the lowest energy state. Some molecules, on the other hand, have many rotatable bonds and their global minimum can only be approximated.[14]

text: Molecular length and rigidity[edit]

text: Neuromuscular blocking agents need to fit in a space close to 2 nanometres, which resembles the molecular length of decamethonium.[13] Some molecules of decamtehonium congeners may bind only to one receptive site. Flexible molecules have a greater chance of fitting receptive sites. However, the most populated conformation may not be the best-fitted one. Very flexible molecules are, in fact, weak neuromuscular inhibitors with flat dose-response curves. On the other hand, stiff or rigid molecules tend to fit well or not at all. If the lowest-energy conformation fits, the compound has high potency because there is a great concentration of molecules close to the lowest-energy conformation. Molecules can be thin but yet rigid.[14] Decamethonium for example needs relatively high energy to change the N-N distance.[13]

text: In general, molecular rigidity contributes to potency, while size affects whether a muscle relaxant shows a polarizing or a depolarizing effect.[4] Cations must be able to flow through the trans-membrane tube of the ion-channel to depolarize the endplate.[14] Small molecules may be rigid and potent but unable to occupy or block the area between the receptive sites.[4] Large molecules, on the other hand, may bind to both receptive sites and hinder depolarizing cations independent of whether the ion-channel is open or closed below. Having a lipophilic surface pointed towards the synapse enhances this effect by repelling cations. The importance of this effect varies between different muscle relaxants and classifying depolarizing from non-depolarizing blocks is a complex issue. The onium heads are usually kept small and the chains connecting the heads usually keep the N-N distance at 10 N or O atoms. Keeping the distance in mind the structure of the chain can vary (double bonded, cyclohexyl, benzyl, etc.)[14]

text: Succinylcholine has a 10-atom distance between its N atoms, like decamethonium. Yet it has been reported that it takes two molecules, as with acetylcholine, to open one nicotinic ion channel. The conformational explanation for this is that each acetylcholine moiety of succinylcholine prefers the gauche (bent, cis) state. The attraction between the N and O atoms is greater than the onium head repulsion. In this most populated state, the N-N distance is shorter than the optimal distance of ten carbon atoms and too short to occupy both receptive sites. This similarity between succinyl- and acetyl-choline also explains its acetylcholine-like side-effects.[14] Comparing molecular lengths, the pachycurares dimethyltubocurarine and d-tubocurarine both are very rigid and measure close to 1.8 nm in total length. Pancuronium and vecuronium measure 1.9 nm, whereas pipecuronium is 2.1 nm. The potency of these compounds follows the same rank of order as their length. Likewise, the leptocurares prefer a similar length. Decamethonium, which measures 2 nm, is the most potent in its category, whereas C11 is slightly too long. Gallamine despite having low bulk and rigidity is the most potent in its class, and it measures 1.9 nm.[4][13] Based on this information one can conclude that the optimum length for neuromuscular blocking agents, depolarizing or not, should be 2 to 2.1 nm.[14]

text: The CAR for long-chain bisquaternary tetrahydroisoquinolines like atracurium, cisatracurium, mivacurium, and doxacurium is hard to determine because of their bulky onium heads and large number of rotatable bonds and groups. These agents must follow the same receptive topology as others, which means that they do not fit between the receptive sites without bending.[13] Mivacurium for example has a molecular length of 3.6 nm when stretched out, far from the 2 to 2.1 nm optimum. Mivacurium, atracurium, and doxacurium have greater N-N distance and molecular length than d-tubocurarine even when bent. To make them fit, they have flexible connections that give their onium heads a chance to position themselves beneficially. This bent N-N scenario probably does not apply to laudexium and decamethylene bisatropium, which prefer a straight conformation.[14]

text: Beers and Reich's law[edit]

text: It has been concluded that acetylcholine and related compounds must be in the gauche (bent) configuration when bound to the nicotinic receptor.[15]) Beers and Reich's studies on cholinergic receptors in 1970 showed a relationship affecting whether a compound was muscarinic or nicotinic. They showed that the distance from the centre of the quaternary N atom to the van der Waals extension of the respective O atom (or an equivalent H-bond acceptor) is a determining factor. If the distance is 0.44 nm, the compound shows muscarinic properties—and if the distance is 0.59 nm, nicotinic properties dominate.[16])

text: Rational design[edit]

text: Pancuronium remains one of the few muscle relaxants logically and rationally designed from structure-action / effects relationship data. A steroid skeleton was chosen because of its appropriate size and rigidness. Acetylcholine moieties were inserted to increase receptor affinity. Although having many unwanted side-effects, a slow onset of action and recovery rate it was a big success and at the time the most potent neuromuscular drug available. Pancuronium and some other neuromuscular blocking agents block M2-receptors and therefore affect the vagus nerve, leading to hypotension and tachycardia. This muscarinic blocking effect is related to the acetylcholine moiety on the A ring on pancuronium. Making the N atom on the A ring tertiary, the ring loses its acetylcholine moiety, and the resulting compound, vecuronium, has nearly 100 times less affinity to muscarin receptors while maintaining its nicotinic affinity and a similar duration of action. Vecuronium is, therefore, free from cardiovascular effects.[3] The D ring shows excellent properties validating Beers and Reich's rule with great precision. As a result, vecuronium has the greatest potency and specificity of all mono-quaternary compounds.[14]

text: Potency[edit]

text: Two functional groups contribute significantly to aminosteroidal neuromuscular blocking potency, it is presumed to enable them to bind the receptor at two points. A bis-quaternary two point arrangement on A and D-ring (binding inter-site) or a D-ring acetylcholine moiety (binding at two points intra-site) are most likely to succeed. A third group can have variable effects.[14] The quaternary and acetyl groups on the A and D ring of pipecuronium prevent it from binding intra-site (binding to two points at the same site). Instead, it must bind as bis-quaternary (inter-site).[4] These structures are very dissimilar from acetylcholine and free pipecuronium from nicotinic or muscarinic side-effects linked to acetylcholine moiety. Also, they protect the molecule from hydrolysis by cholinesterases, which explain its nature of kidney excretion. The four methyl-groups on the quaternary N atoms make it less lipophilic than most aminosteroids. This also affects pipecuroniums metabolism by resisting hepatic uptake, metabolism, and biliary excretion. The length of the molecule (2.1 nm, close to ideal) and its rigidness make pipecuronium the most potent and clean one-bulk bis-quaternary. Even though the N-N distance (1.6 nm) is far away from what is considered ideal, its onium heads are well-exposed, and the quaternary groups help to bring together the onium heads to the anionic centers of the receptors without chirality issues.[14]

text: Adding more than two onium heads in general does not add to potency. Though the third onium head in gallamine seems to help position the two outside heads near the optimum molecular length, it can interfere unfavorably and gallamine turns out to be a weak muscle relaxant, like all multi-quaternary compounds. Considering acetylcholine a quaternizing group larger than methyl and an acyl group larger than acetyl would reduce the molecule's potency. The charged N and the carbonyl O atoms are distanced from structures they bind to on receptive sites and, thus, decrease potency. The carbonyl O in vecuronium for example is thrust outward to appose the H-bond donor of the receptive site. This also helps explain why gallamine, rocuronium, and rapacuronium are of relatively low potency.[14] In general, methyl quaternization is optimal for potency but, opposing this rule, the trimethyl derivatives of gallamine are of lower potency than gallamine. The reason for this is that gallamine has a suboptimal N-N distance. Substituting the ethyl groups with methyl groups would make the molecular length also shorter than optimal. Methoxylation of tetrahydroisoquinolinium agents seems to improve their potency. How methoxylation improves potency is still unclear. Histamine release is a common attribute of benzylisoquinolinium muscle relaxants. This problem generally decreases with increased potency and smaller doses. The need for larger doses increases the degree of this side-effect. Conformational or structural explanations for histamine release are not clear.[14]

text: Pharmacokinetics[edit]

text: Metabolism and Hofmann elimination

text: Deacetylating vecuronium at position 3 results in a very active metabolite.[17] In the case of rapacuronium the 3-deacylated metabolite is even more potent than rapacuronium. As long as the D-ring acetylcholine moiety is unchanged they retain their muscle relaxing effect. Mono-quaternary aminosteroids produced with deacylation in position 17 on the other hand are generally weak muscle relaxants.[14] In the development of atracurium the main idea was to make use of Hofmann elimination of the muscle relaxant in vivo. When working with bisbenzyl-isoquinolinium types of molecules, inserting proper features into the molecule such as an appropriate electron withdrawing group then Hofmann elimination should occur at conditions in vivo. Atracurium, the resulting molecule, breaks down spontaneously in the body to inactive compounds and being especially useful in patients with kidney or liver failure. Cis-atracurium is very similar to atracurium except it is more potent and has a weaker tendency to cause histamine release.[3]

text: Structure relations to onset time

text: The effect of structure on the onset of action is not very well known except that the time of onset appears inversely related to potency.[18] In general mono-quaternary aminosteroids are faster than bis-quaternary compounds, which means they are also of lower potency. A possible explanation for this effect is that drug delivery and receptor binding are of a different timescale. Weaker muscle relaxants are given in larger doses so more molecules in the central compartment must diffuse into the effect compartment, which is the space within the mouth of the receptor, of the body. After delivery to the effect compartment then all molecules act quickly.[19] Therapeutically this relationship is very inconvenient because low potency, often meaning low specificity can decrease the safety margin thus increasing the chances of side-effects. In addition, even though low potency usually accelerates onset of action, it does not guaranty a fast onset. Gallamine, for example, is weak and slow. When fast onset is necessary then succinylcholine or rocuronium are usually preferable.[14]

text: Elimination

text: Muscle relaxants can have very different metabolic pathways and it is important that the drug does not accumulate if certain elimination pathways are not active, for example in kidney failure.

text: Adverse effects[edit]

text: Since these drugs may cause paralysis of the diaphragm, mechanical ventilation should be at hand to provide respiration.

text: In addition, these drugs may exhibit cardiovascular effects, since they are not fully selective for the nicotinic receptor and hence may have effects on muscarinic receptors.[8] If nicotinic receptors of the autonomic ganglia or adrenal medulla are blocked, these drugs may cause autonomic symptoms. Also, neuromuscular blockers may facilitate histamine release, which causes hypotension, flushing, and tachycardia.

text: In depolarizing the musculature, suxamethonium may trigger a transient release of large amounts of potassium from muscle fibers. This puts the patient at risk for life-threatening complications, such as hyperkalemia and cardiac arrhythmias.

text: Certain drugs such as aminoglycoside antibiotics and polymyxin and some fluoroquinolones also have neuromuscular blocking action as their side-effect.[20]

text: Estimating effect[edit]

text: Methods for estimating the degree of neuromuscular block include valuation of muscular response to stimuli from surface electrodes, such as in the train-of-four test, wherein four such stimuli are given in rapid succession. With no neuromuscular blockade, the resultant muscle contractions are of equal strength, but gradually decrease in case of neuromuscular blockade.[21] It is recommended during use of continuous-infusion neuromuscular blocking agents in intensive care.[22]

text: Reversal[edit]

text: The effect of non-depolarizing neuromuscular-blocking drugs may be reversed with acetylcholinesterase inhibitors, neostigmine, and edrophonium, as commonly used examples. Of these, edrophonium has a faster onset of action than neostigmine, but it is unreliable when used to antagonize deep neuromuscular block.[23] Acetylcholinesterase inhibitors increase the amount of acetylcholine in the neuromuscular junction, so a prerequisite for their effect is that the neuromuscular block is not complete, because in case every acetylcholine receptor is blocked then it does not matter how much acetylcholine is present.

text: Sugammadex is a newer drug for reversing neuromuscular block by rocuronium in general anaesthesia. It is the first selective relaxant binding agent (SRBA).[24]

text: History[edit]

text: Curare is a crude extract from certain South American plants in the genera Strychnos and Chondrodendron, originally brought to Europe by explorers such as Walter Raleigh[25] It was known in the 19th century to have a paralysing effect, due in part to the studies of scientists like Claude Bernard.[26] D-tubocurarine a mono-quaternary alkaloid was isolated from Chondrodendron tomentosum in 1942, and it was shown to be the major constituent in curare responsible for producing the paralysing effect. At that time, it was known that curare and, therefore, d-tubocurarine worked at the neuromuscular junction. The isolation of tubocurarine and its marketing as the drug Intocostrin led to more research in the field of neuromuscular-blocking drugs. Scientists figured out that the potency of tubocurarine was related to the separation distance between the two quaternary ammonium heads.[2][27]

text: Further research led to the development of synthesized molecules with different curariform effects, depending on the distance between the quaternary ammonium groups. One of the synthesized bis-quaternaries was decamethonium a 10-carbon bis-quaternary compound. Following research with decamethonium, scientists developed suxamethonium, which is a double acetylcholine molecule that was connected at the acetyl end. The discovery and development of suxamethonium lead to a Nobel Prize in medicine in 1957. Suxamethonium showed different blocking effect in that its effect was achieved more quickly and augmented a response in the muscle before block. Also, tubocurarine effects were known to be reversible by acetylcholinesterase inhibitors, whereas decamethonium and suxamethonium block were not reversible.[2][3]

text: Another compound malouétine that was a bis-quaternary steroid was isolated from the plant Malouetia bequaertiana and showed curariform activity. This led to the synthetic drug pancuronium, a bis-quaternary steroid, and subsequently other drugs that had better pharmacological properties.[2][28] Research on these molecules helped improve understanding of the physiology of neurons and receptors.


document_title: U.S. history of alcohol minimum purchase age by state

question_text: when was maryland drinking age changed to 21

text: The alcohol laws of the United States regarding minimum age for purchase have changed over time.  This history is given in the table below.  Unless otherwise noted, if different alcohol categories have different minimum purchase ages, the age listed below is set at the lowest age given (e.g. if the purchase age is 18 for beer and 21 for wine or spirits, as was the case in several states, the age in the table will read as "18", not "21").  In addition, the purchase age is not necessarily the same as the minimum age for consumption of alcoholic beverages, although they have often been the same.

text:
As one can see in the table below, there has been much volatility in the states' drinking ages since the
repeal of Prohibition in 1933.  Shortly after the ratification of the 21st amendment in December, most states set their purchase ages at 21 since that was the voting age at the time. Most of these limits remained constant until the early 1970s.  From 1969 to 1976, some 30 states lowered their purchase ages, generally to 18. This was primarily because the voting age was lowered from 21 to 18 in 1971 with the 26th amendment. Many states started to lower their minimum drinking age in response, most of this occurring in 1972 or 1973.[1][2][3] Twelve states kept their purchase ages at 21 since repeal of Prohibition and never changed them.

text: From 1976 to 1983, several states voluntarily raised their purchase ages to 19 (or, less commonly, 20 or 21), in part to combat drunk driving fatalities.[citation needed] In 1984, Congress passed the National Minimum Drinking Age Act, which required states to raise their ages for purchase and public possession to 21 by October 1986 or lose 10% of their federal highway funds. By mid-1988, all 50 states and the District of Columbia had raised their purchase ages to 21 (but not Puerto Rico, Guam, or the Virgin Islands, see Additional Notes below). South Dakota and Wyoming were the final two states to comply with the age 21 mandate. The current drinking age of 21 remains a point of contention among many Americans, because of it being higher than the age of majority (18 in most states) and higher than the drinking ages of most other countries. The National Minimum Drinking Age Act is also seen as a congressional sidestep of the tenth amendment. Although debates have not been highly publicized, a few states have proposed legislation to lower their drinking age,[4] while Guam has raised its drinking age to 21 in July 2010.[5]

text:
State
Pre-Prohibition(prior to 1919)
Post-Prohibition(after 1933)
1970s / 26th Amendment(adopted in 1971)
1980s / Drinking Age Act of 1984
21st century

Alabama

Pre 1881:None1881:21 (none with consent of parent)[6]
21
1975:Lowered to 19[7]
1986:Raised to 21[8]
21  (no one underage is allowed consumption Section 28-1)

Alaska

?
21[7]
1970:Lowered to 19[9]
1984:Raised to 21 with grandfather clause (if born before January 1, 1965)[10][11]
21

Arizona

?
21[11]
1972:Lowered to 19[12]
1985:Raised to 21[8]
21

Arkansas

Pre 1925:None[7]1925:21[7]
21
21[13]
21[8]
21

California

Pre 1891:Regulated by municipality/county (common age was 16)[14][15][16]1891:18 (statewide)[17]
1933:21[7]
21
21[8]
21 (except small amounts for religious ceremonies)

Colorado

None[11]
1945:18: for beer21: for wine and liquor[7]
18[18]
Raised to 21 in 1987[8]
21

Connecticut

?
21[11]
1972:Lowered to 18[19]
1982:Raised to 191983:Raised to 201985:Raised to 21[20]
21 (exemptions: (1) a person over age eighteen who is an employee or permit holder under section 30-90a and who possesses alcoholic liquor in the course of such person's employment or business, (2) a minor who possesses alcoholic liquor on the order of a practicing physician, or (3) a minor who possesses alcoholic liquor while accompanied by a parent, guardian or spouse of the minor, who has attained the age of twenty-one. Nothing in this subsection shall be construed to burden a person's exercise of religion under section 3 of article first of the Constitution of the state in violation of subsection (a) of section 52-571b.[21]

Delaware

?
21[11]
1972:Lowered to 20
1984:Raised to 21[8]
21

District of Columbia

?
18: for beer and wine[11]21: for liquor[22][23]
18: for beer and wine[23]21: for liquor
1986:Raised to 21 with grandfather clause.[24][25]
21

Florida

?
18[7]
1980:19[26]
1985:Raised to 21 with grandfather clause[26]
21[27]

Georgia

?
21[11]
1972: Lowered to 18[12]
1984:Raised to 19[13]1985:Raised to 20[13]1986:Raised to 21[13]
21

Hawaii

?
21[7]
1972:Lowered to 18
1986:Raised to 21[8]
21

Idaho

?
20: for beer[28][29]21: for wine and liquor[11][30]
1972:Lowered to 19 (all)[31]
1987:Raised to 21 in 1987 (Apr 11) with grandfather clause[8][32]
21

Illinois

1872:Age of majority (none with written consent of parent)[33]
pre 1961: Age of majority      1961:  Raised to 21[34]
1973:Lowered to 19: for beer and wine21: for liquor[35]
1980:Raised to 21[36]
21

Indiana

?
Post-1934:21[7]
21[13]
21[8]
21

Iowa

?
21[7]
1972:Lowered to 19 in 1972 (Jul 1)1973:Lowered to 18 in 1973 (Jul 1)1978:Raised to 19 in 1978 (Jul 1)[37]
1986:Raised to 21 in 1986 (Jul 1) with grandfather clause.[13][37]
21

Kansas

?
1949:18: for beer and wine with less than 4% ABV21: for liquor[7]
18: for beer and wine with less than 4% ABV[13]21: for beer and wine with 4% ABV or more[13]21: for liquor[13][18]
1985:Raised to 21[8]
21 (However, anyone under 21 may consume cereal malt beverages with parental supervision on their own property)

Kentucky

?
1938:21[7]
21[13]
21[8]
21

Louisiana

?
As of 1948:18
18[18]
1987:Raised to 21 de jure in 1987,[8]but de facto age was still 18 until 1995 due to a sale loophole.1995:De facto age raised to 21 in 1995 when loophole was closed.[38]1996:In 1996, briefly lowered by Louisiana Supreme Court to 18 until it reversed its decision, raising to 21 three months later.[39]Other exceptions still remain.[40]
21 (Exceptions to state law include:[41]
For an established religious purpose;When a person under twenty-one years of age is accompanied by a parent, spouse, or legal guardian twenty-one years of age or older;For medical purposes when purchased as an over the counter medication, or when prescribed or administered by a licensed physician, pharmacist, dentist, nurse, hospital, or medical institution;In a private residence, which shall include a residential dwelling and up to twenty contiguous acres, on which the dwelling is located, owned by the same person who owns the dwelling;The sale, handling, transport, or service in dispensing of any alcoholic beverage pursuant to lawful ownership of an establishment or to lawful employment of a person under twenty-one years of age by a duly licensed manufacturer, wholesaler, or retailer of beverage alcohol.)

Maine

?
21[7]1969:Lowered to 20
1972:Lowered to 18[12]1977:Raised to 20[8][42]
1985:Raised to 21[8]
21

Maryland

?
21[7]
1974:Lowered to 18: for beer and wine21: for liquor[43][44]
1982:Raised to 21 with grandfather clause for those born June 30, 1964 or earlier[45][8][46]
21 (however anyone can drink when parents, spouses, teachers are present)

Massachusetts

?
21[11]
1973:Lowered to 181979:Raised to 20 in 1979 (Apr 16)[47][48][49]
Raised to 21 in 1985[8]
21

Michigan

?
21[7]
1972:Lowered to 18 in 1972 (Jan 1)[50]
1978:Raised to 19 in 1978 (Dec 3)[51][52]1978:Raised to 21 in 1978 (Dec 21), 18 days later.[8]First state to raise age to 21 since it was lowered
21

Minnesota

?
21[11]
1973:Lowered to 18 (June 1)1976:Raised to 19 (Sept 1)[53]First state to raise age after lowering.

1986:Raised to 21[54]
21

Mississippi

?
1966:18: for beer and wine21: for liquor[7](alcohol not legalized until 1966)
18[18]
Raised to 21 in 1986[8]
21

Missouri

?
1945:21[7]
21
21[8]
21

Montana

?
21[11]
1971:Lowered to 19[55]1973:Lowered to 18[56][57]1979:Raised to 19
1987:Raised to 21[8][58]
21

Nebraska

?
21[59]1969:Lowered to 20
1972:Lowered to 19[59]
1980:Raised to 20[13]1985:Raised to 21[13]
21

Nevada

?
1933:21[7]
21
21[8]
21

New Hampshire

?
21[11]
1973:Lowered to 18[60]1979:Raised to 20
1985:Raised to 21[8][20]
21

New Jersey

Before 1880:NonePost-1880:18 (penalties only against businesses)[61][62][63]
21[citation needed]
1973:Lowered to 18[12]
1980:Raised to 191983:Raised to 21[8][64]
21

New Mexico

?
1934:21[7]
21[13]
21[8]
21

New York

21
18[65]
18
1982:Raised to 19 in 1982 (Dec)1985:Raised to 21 in 1985 (Dec)[20][66][67]
21

North Carolina

?
18[11]
18: for beer and wine[18] 21: for liquor
1983:19: for beer and wine 21: for liquor1986:Raised to 21 in 1986 (Sep 1)[8][25]
21

North Dakota

?
1936:21[7]
21[13]
21[68]
21

Ohio

?
1935:18: for 3.2% ABW beer21: for beer stronger than 3.2% ABW, wine and liquor[69]
18: for 3.2% ABW beer21: for beer stronger than 3.2% ABW, wine and liquor
1982 (Aug. 19 to Oct. 1):19: for 3.2% ABW beer[13]21: for beer stronger than 3.2% ABW, wine and liquor[13]1982 (From Oct. 1):19: beer21: wine and liquor[70]1988:21[13]
21 (However, anyone can drink with parents or legal-age spouse)

Oklahoma

?
Men:21Women:18: 3.2% ABW beer21: for beer stronger than 3.2% ABW, wine and liquor[71]
1976:Lowered to 18 (for 3.2% ABW beer) for both sexes in 1976 (Dec)[72]Last state to lower the drinking age.
1983:Raised to 21[11][73]
21

Oregon

?
1933:21[7]
21
21[8]
21

Pennsylvania

?
1935:21[7]
21
21[8][52]
21

Rhode Island

?
21[11]
1970:Lowered to 18[12][74]
1980:Raised to 191981:Raised to 201984:Raised to 21[20]
21

South Carolina

21[75]
1935:18: for beer and wine21: for liquor[7]
18: for beer and wine[18]21: for liquor
1984:19: for beer and wine[7]21: for liquor1986:Raised to 21[8]
21

South Dakota

?
1934:21 (all)1939:Lowered to 18: for 3.2% beerRaised to 19: for 3.2% beer[76]
1972:18: for beer and wine21: for liquor
1984:19: for beer and wine21: for liquor[8]1988:Raised to 21[58]
21

Tennessee

Pre 1881:None1881:21[77]
21[7]1964:Lowered to 18[7]
1979:Raised to 19
1984:Raised to 21[8]
21

Texas

Pre 1909:21None (with written permission of parent or guardian)Post 1909:21[78][79]
21[7]
1973:Lowered to 18[80]
1981:Raised to 19[81]1986:Raised to 21 in 1986 (Sep 1)[8][25]
21

Utah

?
1935:21[7]
21[13]
21[8]
21

Vermont

?
21[7]
1971:Lowered to 18[82][83]
1986:Raised to 21[20][83]
21

Virginia

?
21[84]
1974:Lowered to 18: for beer and wine(21: for liquor remained)[84]
1981:Raised to 19 for off-premises consumption1983:Raised to 19 (all beer)1985:Raised to 21[84]
21

Washington

Age of majoritysince 1877[85]
21[citation needed]
21
21[8]
21

West Virginia

?
18: for beer and wine 21: for liquor[11]
1972:Lowered to 18 (all)[86]
1983:Raised to 19(& 21 for non-residents)[8][42]1986:Raised to 21[8]
21

Wisconsin

1839–1866:18: for wine and liquorNone: for beerPost-1866:21 (all)[87]
18: for beer21: for wine and spirits1957:21: for residents of bordering states with age limit 21.[88]1963:Raised to 21 (off-premises beer sales, remained 18 for on-premises).[88]
1972:Lowered to 18 (all) in 1972 (Mar)[88]1977:Border state restriction lifted.[88]
1984:Raised to 191986:Raised to 21 (September 1, 1986)[88]
21 (however anyone can drink when parents, spouses, teachers are present)[citation needed]

Wyoming

?
21[7]
1973:Lowered to 19
1988:Raised to 21 in 1988 (Jul 1)[89][90]Last state to raise de jure drinking age to 21
21

American Samoa

?
?
?
21?
21[91]

Northern Mariana Islands

–
–
?
21?
21[92]

Puerto Rico

?
18
18
Kept at 18despite highway fundingpenalty under Drinking Age Act.
18[93]

Virgin Islands

?
?
?
18
18[94]

Guam

?
21?
18
18
Raised to 21 in 2010[5]

text: Additional notes[edit]

text:
Contrary to popular belief, since the National Minimum Drinking Age Act of 1984, not all states specifically prohibit minors' and young adults' consumption of alcohol in private settings.  That is because the federal law is concerned only with purchase and public possession, not private consumption, and contains several exceptions. As of January 1, 2007, 14 states and the District of Columbia ban underage consumption outright, 19 states do not specifically ban underage consumption outright, and 17 states have family member or location exceptions to their underage consumption laws. Federal law explicitly provides for religious, medical, employment and private club possession exceptions; as of 2005, 31 states have family member or location exceptions to their underage possession laws.[40]
In the 1960s the age for buying or drinking beer and wine in the District of Columbia (Washington, D.C.) was 18; the age for hard liquor was 21.[22][23] Residents from Virginia and Maryland would often drive to D.C. to obtain alcohol. In Louisiana, the 1987 law raising the age from 18 to 21 was deliberately written solely to comply with the National Minimum Drinking Age Act of 1984 to avoid losing highway funding, while still allowing 18- to 20-year-olds to drink as before.  Not only did it still allow 18- to 20-year-olds to consume in private, it contained a major loophole allowing bars and stores to sell alcohol to 18- to 20-year-olds without penalty (despite purchase being technically illegal) which meant that the de facto age was still 18.[38] In other words, the drinking age was 21 only on paper. This loophole was closed in 1995, but in 1996 the Louisiana Supreme Court declared a drinking age of 21 unconstitutional.[38]  That briefly lowered the de jure purchase age to 18, causing an uproar which prompted the Louisiana Supreme Court to reverse its decision, raising the age to 21 three months later.[39] Other exceptions still remain to this day, including drinking in a private residence,[40] and Louisiana still has some of the most liberal general alcohol laws of any state.
Some states were "dry" well before national Prohibition was enacted in 1919, in some cases since achieving statehood.  Also, some states did not become fully "wet" until several years after the repeal of Prohibition in 1933 (e.g. Mississippi in 1966).  Since 1966, all states and territories of the USA have been "wet", but dry counties and towns still exist in some states.