Selective relaxant binding agents (SRBAs ) are a new class ofdrugs that selectively encapsulates and bindsneuromuscular blocking agents (NMBAs). The first drug introduction of an SRBA issugammadex . SRBAs exert achelating action that effectively terminates an NMBA ability to bind tonicotinic receptors .[ 1]
Examples of SRBAs include:
1. Sugammadex is a modified gamma cyclodextrin that specifically encapsulates and binds the aminosteroid NMBAs: affinity is highest forrocuronium , followed byvecuronium , and relatively low affinity forpancuronium .
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] [ 5]
The discovery of SRBA as a new class of drug is the result of work done by Organon laboratories at theNewhouse research site inScotland .Cyclodextrins were explored as a means to solubilize rocuronium bromide (asteroidal NMBA) in a neutral aqueous solution. Upon creating numerous modified cyclodextrins, one particularmolecule 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 . {{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 . {{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 Ambutonium bromide Anisodamine Anisodine Antihistamines (first-generation) (e.g.,brompheniramine ,buclizine ,captodiame ,chlorphenamine (chlorpheniramine) ,cinnarizine ,clemastine ,cyproheptadine ,dimenhydrinate ,dimetindene ,diphenhydramine ,doxylamine ,meclizine ,mequitazine ,perlapine ,phenindamine ,pheniramine ,phenyltoloxamine ,promethazine ,propiomazine ,triprolidine )AQ-RA 741 Atropine Atropine methonitrate Atypical antipsychotics (e.g.,clozapine ,fluperlapine ,olanzapine (+fluoxetine ),rilapine ,quetiapine ,tenilapine ,zotepine )Benactyzine Benzatropine (benztropine) Benzilone Benzilylcholine mustard Benzydamine Bevonium BIBN 99 Biperiden Bornaprine 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 Cloperastine CS-27349 Cyclobenzaprine Cyclopentolate Darifenacin DAU-5884 Desfesoterodine Dexetimide DIBD Dicycloverine (dicyclomine) Dihexyverine Difemerine Diphemanil metilsulfate Ditran Drofenine EA-3167 EA-3443 EA-3580 EA-3834 Emepronium bromide Etanautine Etybenzatropine (ethybenztropine) Fenpiverinium Fentonium bromide Fesoterodine Flavoxate Glycopyrronium bromide (+beclometasone/formoterol ,+indacaterol ,+neostigmine )Hexahydrodifenidol Hexahydrosiladifenidol Hexbutinol Hexocyclium Himbacine HL-031,120 Homatropine Imidafenacin Ipratropium bromide (+salbutamol )Isopropamide J-104,129 Hyoscyamine Mamba toxin 3 Mamba toxin 7 Mazaticol Mebeverine Meladrazine Mepenzolate Methantheline Methoctramine Methylatropine Methylhomatropine Methylscopolamine Metixene Muscarinic toxin 7 N-Ethyl-3-piperidyl benzilate N-Methyl-3-piperidyl benzilate Nefopam Octatropine methylbromide (anisotropine methylbromide) Orphenadrine Otenzepad (AF-DX 116) Otilonium bromide Oxapium iodide Oxitropium bromide Oxybutynin Oxyphencyclimine Oxyphenonium bromide PBID PD-102,807 PD-0298029 Penthienate Pethidine pFHHSiD Phenglutarimide Phenyltoloxamine Pipenzolate bromide Piperidolate Pirenzepine Piroheptine Pizotifen Poldine Pridinol Prifinium bromide Procyclidine Profenamine (ethopropazine) Propantheline bromide Propiverine Quinidine 3-Quinuclidinyl thiochromane-4-carboxylate Revefenacin Rociverine RU-47,213 SCH-57,790 SCH-72,788 SCH-217,443 Scopolamine (hyoscine) Scopolamine butylbromide (hyoscine butylbromide) Silahexacyclium Sofpironium bromide Solifenacin SSRIs Tooltip Selective serotonin reuptake inhibitors (e.g.,femoxetine ,paroxetine )Telenzepine Terodiline Tetracyclic antidepressants (e.g.,amoxapine ,maprotiline ,mianserin ,mirtazapine )Tiemonium iodide Timepidium bromide Tiotropium bromide Tiquizium bromide Tofenacin Tolterodine Tricyclic antidepressants (e.g.,amitriptyline (+perphenazine ),amitriptylinoxide ,butriptyline ,cidoxepin ,clomipramine ,desipramine ,desmethyldesipramine ,dibenzepin ,dosulepin (dothiepin) ,doxepin ,imipramine ,lofepramine ,nitroxazepine ,northiaden (desmethyldosulepin) ,nortriptyline ,protriptyline ,quinupramine ,trimipramine )Tridihexethyl Trihexyphenidyl Trimebutine Tripitamine (tripitramine) Tropacine Tropatepine Tropicamide Tropine benzilate Trospium chloride Typical antipsychotics (e.g.,chlorpromazine ,chlorprothixene ,cyamemazine (cyamepromazine) ,loxapine ,mesoridazine ,thioridazine )Umeclidinium bromide (+vilanterol )WIN-2299 Xanomeline Zamifenacin
Precursors (andprodrugs )
nAChRs Tooltip Nicotinic acetylcholine receptors
Agonists 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 Acetylcholine Altinicline Anabasine Anatabine Anatoxin-a AR-R17779 Bephenium hydroxynaphthoate Butinoline Butyrylcholine Carbachol Choline Choline m-bromophenyl ether Cotinine Cytisine Decamethonium Desformylflustrabromine Dianicline Dimethylphenylpiperazinium Epibatidine Epiboxidine Ethanol (alcohol) Ethoxysebacylcholine EVP-4473 EVP-6124 Galantamine GTS-21 Ispronicline Ivermectin JNJ-39393406 Levamisole Lobeline MEM-63,908 (RG-3487) Morantel Nicotine (tobacco )NS-1738 PHA-543,613 PHA-709,829 PNU-120,596 PNU-282,987 Pozanicline Pyrantel Rivanicline RJR-2429 Sazetidine A SB-206553 Sebacylcholine SIB-1508Y SIB-1553A SSR-180,711 Suberyldicholine Suxamethonium (succinylcholine) Suxethonium (succinyldicholine) TC-1698 TC-1734 TC-1827 TC-2216 TC-5214 TC-5619 TC-6683 Tebanicline Tribendimidine Tropisetron UB-165 Varenicline WAY-317,538 XY-4083 Antagonists NAMs Tooltip negative allosteric modulators )
Precursors (andprodrugs )
