title: Preclinical pharmacology of sugammadex.
abstract: Since the introduction of nondepolarizing neuromuscular blocking agents, acetylcholinesterase inhibitors have been used to increase the speed of recovery from neuromuscular blockade. The major disadvantages of acetylcholinesterase inhibitors are their lack of activity against profound neuromuscular blockade and their activity outside the neuromuscular junction resulting in unwanted side effects, requiring cotreatment with a muscarinic antagonist. An alternative to acetylcholinesterase inhibitors is the encapsulating agent sugammadex. This agent has been specifically designed to encapsulate the steroidal neuromuscular blocking agents rocuronium and vecuronium. This review describes the effects of sugammadex in in vitro tissue and in vivo animal experiments. The encapsulation approach allows reversal of any degree of neuromuscular blockade because the dose of sugammadex can be adjusted to encapsulate sufficient neuromuscular blocking molecules to cause effective reversal. Because this interaction is a drug-drug interaction, reversal can be achieved very fast but is limited by the circulation time. Sugammadex is also effective against neuromuscular blockade under conditions with reduced acetylcholine release, which potentiate the action of neuromuscular blocking agents. Sugammadex does not cause cholinergic side effects, preventing the need of coadministration of muscarinic antagonists. Because of these properties, sugammadex has the potential to become a very useful drug for the management of neuromuscular blockade.
authors.affiliation: Department of Pharmacology, Schering-Plough Corporation, Newhouse, ML1 5SH Scotland, United Kingdom. ton.bom@spcorp.com
authors.forename: Anton
authors.initials: A
authors.lastname: Bom
authors.forename: Frank
authors.initials: F
authors.lastname: Hope
authors.forename: Samantha
authors.initials: S
authors.lastname: Rutherford
authors.forename: Karen
authors.initials: K
authors.lastname: Thomson
mesh_terms: D000732:Androstanols / Q000037:antagonists & inhibitors; D000762:Anesthesia Recovery Period; D000818:Animals; D002151:Calorimetry; D002626:Chemistry, Pharmaceutical; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects / Q000294:innervation; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D008657:Metabolic Clearance Rate; D051379:Mice; D019148:Neuromuscular Blockade / Q000009:adverse effects / Q000379:methods; D009469:Neuromuscular Junction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors*; D000077123:Rocuronium; D012449:Safety; D013045:Species Specificity; D000077122:Sugammadex; D014018:Tissue Distribution / Q000502:physiology; D017186:Titrimetry; D014673:Vecuronium Bromide / Q000037:antagonists & inhibitors; D047408:gamma-Cyclodextrins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000732:Androstanols; D002800:Cholinesterase Inhibitors; D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D014673:Vecuronium Bromide; D000077123:Rocuronium