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Selective relaxant binding agents (SRBAs ) are a new class of drugs that selectively encapsulates and binds neuromuscular blocking agents (NMBAs). The first drug introduction of an SRBA is sugammadex . . SRBAs exert a chelating action that effectively terminates an NMBA ability to bind to nicotinic receptors .[ 1]
Examples of SRBAs include:
1. Sugammadex is a modified gamma cyclodextrin that specifically encapsulates and binds the aminosteroid NMBAs: affinity is highest for rocuronium , followed by vecuronium , and relatively low affinity for pancuronium .
2. Adamgammadex is also a modified gamma-cyclodextrin, with acetyl-amino groups replacing the carboxylic acid groups of sugammadex. Early research suggests it may have a lower incidence of adverse reactions than sugammadex [ 2] [ 3]
3. Calabadion 1 and calabadion 2 are cucurbituril molecules with high binding affinity for both aminosteroid and benzylisoquinoline muscle relaxants.[ 4] Calabadion 2 has 89 times the affinity for rocuronium than does sugammadex.[ 5]
The discovery of SRBA as a new class of drug is the result of work done by Organon laboratories at the Newhouse research site in Scotland . Cyclodextrins were explored as a means to solubilize rocuronium bromide (a steroidal NMBA) in a neutral aqueous solution. Upon creating numerous modified cyclodextrins, one particular molecule was found to possess extremely high affinity for the rocuronium molecule. Originally known as Org25969, it is now generically named sugammadex sodium.
^ Naguib, Mohamed; Brull, Sorin J (January 2009). "Sugammadex: a novel selective relaxant binding agent" . Expert Review of Clinical Pharmacology . 2 (1): 37–53. doi :10.1586/17512433.2.1.37 . ISSN 1751-2433 . PMID 24422770 . S2CID 40625075 .
^ Jiang Y, Zhang Y, Zhu Z, Huang Y, Zhou D, Liu J, Li C, Chen X, Kang D, Wang S, Liu J, Liu B, Zhang W. (25 Nov 2022). "Comparison of the Efficacy and Safety of Adamgammadex with Sugammadex for Reversal of Rocuronium-Induced Neuromuscular Block: Results of a Phase II Clinical Trial" . J Clin Med . 11 (23): 6951. doi :10.3390/jcm11236951 . PMC 9738056 . PMID 36498526 . {{cite journal }}
: CS1 maint: multiple names: authors list (link )
^ Zhang Y, Jiang Y, Lei Q, Li C, Jin S, Wang Q, Huang Y, Li Y, Hong Y, Wang S, Lin H, Li H, Ou Y, Zou X, Sun Q, Guo Q, Chen Z, Min S, Qi Y, Jie Q, Liu J, Liu B, Zhang W. (Jan 2024). "Phase III clinical trial comparing the efficacy and safety of adamgammadex with sugammadex for reversal of rocuronium-induced neuromuscular block" . Br J Anaesth . 132 (1): 45–52. doi :10.1016/j.bja.2023.10.022 . PMID 38007377 . Retrieved 11 April 2024 . {{cite journal }}
: CS1 maint: multiple names: authors list (link )
^ Hoffmann U, Grosse-Sundrup M, Eikermann-Haerter K, Zaremba S, Ayata C, Zhang B, Ma D, Isaacs L, Eikermann M. (August 2013). "Calabadion: A new agent to reverse the effects of benzylisoquinoline and steroidal neuromuscular-blocking agents" . Anesthesiology . 119 (2): 317–325. doi :10.1097/ALN.0b013e3182910213 . PMID 23549405 . Retrieved 11 April 2024 . {{cite journal }}
: CS1 maint: multiple names: authors list (link )
^ Haerter F, Simons JC, Foerster U, Moreno Duarte I, Diaz-Gil D, Ganapati S, Eikermann-Haerter K, Ayata C, Zhang B, Blobner M, Isaacs L, Eikermann M. (Dec 2015). "Comparative Effectiveness of Calabadion and Sugammadex to Reverse Non-depolarizing Neuromuscular-blocking Agents" . Anesthesiology . 123 (6): 1337–1349. doi :10.1097/ALN.0000000000000868 . PMC 4679413 . PMID 26418697 . {{cite journal }}
: CS1 maint: multiple names: authors list (link )
mAChRs Tooltip Muscarinic acetylcholine receptors
Agonists Antagonists
3-Quinuclidinyl benzilate
4-DAMP
Aclidinium bromide (+formoterol )
Abediterol
AF-DX 250
AF-DX 384
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Anisodamine
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BIBN 99
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Camylofin
CAR-226,086
CAR-301,060
CAR-302,196
CAR-302,282
CAR-302,368
CAR-302,537
CAR-302,668
Caramiphen
Cimetropium bromide
Clidinium bromide
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CS-27349
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DAU-5884
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EA-3167
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HL-031,120
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J-104,129
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PD-102,807
PD-0298029
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RU-47,213
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WIN-2299
Xanomeline
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Precursors (and prodrugs )
nAChRs Tooltip Nicotinic acetylcholine receptors
Agonists (and PAMs Tooltip positive allosteric modulators )
5-HIAA
6-Chloronicotine
A-84,543
A-366,833
A-582,941
A-867,744
ABT-202
ABT-418
ABT-560
ABT-894
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AR-R17779
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EVP-4473
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JNJ-39393406
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NS-1738
PHA-543,613
PHA-709,829
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PNU-282,987
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RJR-2429
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SB-206553
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SIB-1508Y
SIB-1553A
SSR-180,711
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TC-1698
TC-1734
TC-1827
TC-2216
TC-5214
TC-5619
TC-6683
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Tropisetron
UB-165
Varenicline
WAY-317,538
XY-4083
Antagonists (and NAMs Tooltip negative allosteric modulators )
Precursors (and prodrugs )