Neuromuscular and vagal blocking actions of pancuronium bromide, its metabolites, and vecuronium bromide (Org NC45) and its potential metabolites in the anaesthetized cat. 1983

I G Marshall, and A J Gibb, and N N Durant

The neuromuscular and cardiac vagus blocking actions of pancuronium, vecuronium (Org NC45) and their respective potential hydroxy metabolites have been studied in the chloralose-anaesthetized cat. Pancuronium was three times more potent as a neuromuscular blocker than its 3-hydroxy derivative, 20 times more potent than the 17-hydroxy derivative and 45 times more potent than the 3,17-dihydroxy derivative. The vagal:neuromuscular block ratios measured at 50% inhibition for these compounds were pancuronium 3.0, 3-hydroxy derivative 6.4, 17-hydroxy derivative 1.1 and 3,17-dihydroxy derivative 0.36 (a value greater than unity indicated greater potency at the neuromuscular junction). Vecuronium was 1.4 times more potent than its 3-hydroxy derivative, 24 times more potent than the 17-hydroxy derivative and 72 times more potent than the 3,17-dihydroxy derivative as a neuromuscular blocker. The vagal:neuromuscular block ratios were vecuronium 79.8, 3-hydroxy derivative 40.4, 17-hydroxy derivative 0.85 and 3,17-dihydroxy derivative 0.15. The 3-hydroxy derivative of vecuronium, the most likely first metabolite of vecuronium, thus possessed only slightly less neuromuscular blocking potency than vecuronium, coupled with a high safety margin between neuromuscular and vagal blocking doses. In addition, the time-course of its action was not different from that of vecuronium. Thus, it is concluded that this potential metabolite is unlikely to give rise to tachycardia in man. It is unlikely that the 17-hydroxy and 3,17-dihydroxy derivatives of vecuronium would be produced in sufficiently great quantities by metabolism from vecuronium to result in either tachycardia or residual neuromuscular blockade.

UI MeSH Term Description Entries
D008297 Male Males
D009466 Neuromuscular Blocking Agents Drugs that interrupt transmission of nerve impulses at the skeletal neuromuscular junction. They can be of two types, competitive, stabilizing blockers (NEUROMUSCULAR NONDEPOLARIZING AGENTS) or noncompetitive, depolarizing agents (NEUROMUSCULAR DEPOLARIZING AGENTS). Both prevent acetylcholine from triggering the muscle contraction and they are used as anesthesia adjuvants, as relaxants during electroshock, in convulsive states, etc. Neuromuscular Blocker,Neuromuscular Blocking Agent,Neuromuscular Blockers,Agent, Neuromuscular Blocking,Agents, Neuromuscular Blocking,Blocker, Neuromuscular,Blockers, Neuromuscular,Blocking Agent, Neuromuscular,Blocking Agents, Neuromuscular
D009469 Neuromuscular Junction The synapse between a neuron and a muscle. Myoneural Junction,Nerve-Muscle Preparation,Junction, Myoneural,Junction, Neuromuscular,Junctions, Myoneural,Junctions, Neuromuscular,Myoneural Junctions,Nerve Muscle Preparation,Nerve-Muscle Preparations,Neuromuscular Junctions,Preparation, Nerve-Muscle,Preparations, Nerve-Muscle
D010197 Pancuronium A bis-quaternary steroid that is a competitive nicotinic antagonist. As a neuromuscular blocking agent it is more potent than CURARE but has less effect on the circulatory system and on histamine release. Pancuronium Bromide,Pancuronium Curamed,Pancuronium Organon,Pavulon,Bromide, Pancuronium
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D014630 Vagus Nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Cranial Nerve X,Pneumogastric Nerve,Tenth Cranial Nerve,Nerve X,Nervus Vagus,Cranial Nerve, Tenth,Cranial Nerves, Tenth,Nerve X, Cranial,Nerve Xs,Nerve, Pneumogastric,Nerve, Tenth Cranial,Nerve, Vagus,Nerves, Pneumogastric,Nerves, Tenth Cranial,Nerves, Vagus,Pneumogastric Nerves,Tenth Cranial Nerves,Vagus Nerves,Vagus, Nervus

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