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Amit Prabhakar, Alan D Kaye, Melville Q Wyche, Orlando J Salinas, Kenneth Mancuso, Richard D Urman
Pharmacological advances in anesthesia in recent decades have resulted in safer practice and better outcomes. These advances include improvement in anesthesia drugs with regard to efficacy and safety profiles. Although neuromuscular blockers were first introduced over a half century ago, few new neuromuscular blockers and reversal agents have come to market and even fewer have remained as common clinically employed medications. In recent years, newer agents have been studied and are presented in this review...
July 2016: Journal of Anaesthesiology, Clinical Pharmacology
Paul M Heerdt, Hiroshi Sunaga, John J Savarese
PURPOSE OF REVIEW: This review summarizes recent progress in the development of new muscle relaxants that are inactivated by cysteine, and considers the evolving paradigm of selective relaxant binding or degrading agents that can reverse neuromuscular blockade at any time. RECENT FINDINGS: The benzylisoquinoline compound gantacurium is a nondepolarizing muscle relaxant with an ultrashort duration largely determined by the rapid rate at which endogenous L-cysteine binds to, and permanently inactivates, the molecule...
August 2015: Current Opinion in Anaesthesiology
Manuel Martin-Flores, Jonathan Cheetham, Luis Campoy, Daniel M Sakai, Paul M Heerdt, Robin D Gleed
OBJECTIVE: To evaluate whether the ultrashort-acting neuromuscular blocking agent gantacurium can be used to blunt evoked laryngospasm in anesthetized cats and to determine the duration of apnea without hemoglobin desaturation. ANIMALS: 8 healthy adult domestic shorthair cats. PROCEDURES: Each cat was anesthetized with dexmedetomidine and propofol, instrumented with a laryngeal mask, and allowed to breathe spontaneously (fraction of inspired oxygen, 1...
March 2015: American Journal of Veterinary Research
John J Savarese, Jeff D McGilvra, Hiroshi Sunaga, Matthew R Belmont, Scott G Van Ornum, Peter M Savard, Paul M Heerdt
BACKGROUND: The ultra-short-acting neuromuscular blocker gantacurium is chemically degraded in vitro by rapid adduction of L-cysteine to its central olefinic double bond. Preliminary data have suggested that exogenous (intravenous) L-cysteine abolishes gantacurium blockade. Two new analogues of gantacurium (CW 002 and CW 011) have been synthesized to undergo slower L-cysteine adduction, yielding intermediate duration. L-cysteine adduction to and antagonism of these novel agents is further defined herein...
July 2010: Anesthesiology
Hiroshi Sunaga, Yi Zhang, John J Savarese, Charles W Emala
BACKGROUND: Neuromuscular blocking agents are an integral component of general anesthesia. In addition to their intended pharmacologic target on skeletal muscle nicotinic receptors, undesirable airway effects (i.e., bronchoconstriction) can result from neuromuscular blocking agents' affinity for airway muscarinic receptors. We questioned whether two new members of a bisquaternary nondepolarizing muscle relaxant family, gantacurium and CW002, demonstrated detrimental effects of airway muscarinic receptors using an in vivo model in guinea pig airways...
April 2010: Anesthesiology
Mohamed Naguib, Sorin J Brull
PURPOSE OF REVIEW: We review the efficacy and safety of gantacurium and AV002, two novel, investigational fumarate-based nondepolarizing neuromuscular blockers, as well as sugammadex and cysteine, two novel reversal drugs that have no acetylcholinesterase inhibition properties. RECENT FINDINGS: Gantacurium (with a pharmacodynamic profile similar to that of succinylcholine) and AV002 (with an intermediate duration of action) have shown efficacy in animals and, for gantacurium, in humans...
August 2009: Current Opinion in Anaesthesiology
M BayƩs, X Rabasseda, J R Prous
Gateways to Clinical Trials is a guide to the most recent clinical trials reported in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, This issue focuses on the following selection of drugs:[188Re]-HDD; A-179578, adalimumab, AK-602, albumin interferon alfa, alfimeprase, amelubant, anakinra, anti-CD2 MAb, APD-356, aripiprazole, atvogen; Bimatoprost, bimosiamose, BLP-25, brivaracetam; Caspofungin acetate, cilansetron, CMV vaccine (bivalent), conivaptan hydrochloride, Cypher; Darbepoetin alfa, darifenacin hydrobromide, D-D4FC, decitabine, dnaJP1, doranidazole, dronedarone hydrochloride; Efalizumab, efaproxiral sodium, emtricitabine, Endeavor, entecavir, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, etravirine, ezetimibe; Fampridine, fenretinide, ferumoxtran-10, forodesine hydrochloride; Gantacurium chloride, gemi-floxacin mesilate, Glyminox, GW-501516; HBV-ISS, hepavir B, human insulin, HuMax-CD20, hyaluronic acid, HyCAMP; Icatibant, IDEA-070, IGN-311, imatinib mesylate, insulin detemir, insulin glargine, insulin glulisine; Lapatinib, lasofoxifene tartrate, LB-80380, liarozole fumarate, liposome encapsulated doxorubicin, lumiracoxib, LY-570310; MC-1, melatonin, merimepodib, metanicotine, midostaurin; Natalizumab, nicotine conjugate vaccine, NYVAC-HIV C; Patupilone, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pelitinib, Peru-15, pexelizumab, PHP, pimecrolimus, prednisolone sodium metasulfobenzoate; Recombinant alfa1-antitrypsin (AAT), retigabine, rHA influenza vaccine, rifalazil, rofecoxib, rosiglitazone maleate/Metformin hydrochloride, rostaporfin, rosuvastatin calcium, rubitecan; Selenite sodium, semilente insulin, SMP-797, sorafenib; Talampanel, tenofovir disoproxil fumarate, TER-199, tiotropium bromide, torcetrapib, treprostinil sodium, TTA; ValboroPro, valdecoxib, val-mCyd, valtorcitabine dihydrochloride: XP-828L...
January 2005: Methods and Findings in Experimental and Clinical Pharmacology
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