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The efficacy of some bis-pyridinium oximes as antidotes to soman in isolated muscles of several species including man

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Author: Wolthuis, O. · Vanwersch, R.A.P. · Wiel, H.J. van der
Type:article
Date:1981
Institution: Medisch Biologisch Laboratorium TNO
Source:European Journal of Pharmacology, 3, 70, 355-369
Identifier: 229041
Keywords: Biology · 1 (3 carbamoylpyridinio) 1' (2 hydroxyiminomethylpyridinio)dimethyl ether · 1 (4 carbamoylpyridinio) 1' (2 hydroxyiminomethylpyridinio)dimethyl ether · [(3 isobutyryl 1 pyridiniomethyl) (2 hydroxyiminomethyl 1 pyridiniomethyl)] ether · Sarin · Soman · Tubocurarine chloride · Unclassified drug · Animal experiment · Bispyridinium oxime · Diaphragm · Dog · Dose response · Drug comparison · Drug response · Guinea pig · Human cell · In vitro study · Intercostal muscle · Intravenous drug administration · Neuromuscular transmission · Rat · Adult · Aged · Animal · Antidotes · Chorionic Gonadotropin · Comparative Study · Dogs · Electric Stimulation · Female · Guinea Pigs · Human · In Vitro · Male · Middle Age · Neuromuscular Junction · Organophosphorus Compounds · Pralidoxime Compounds · Pyridinium Compounds · Rats · Sarin · Soman · Species Specificity · Synaptic Transmission

Abstract

Previous results had shown that bis-pyridinium oximes, particularly HI-6 are quite effective therapeutically in soman-poisoned rats and mice in vivo and in the rat diaphragm preparation in vitro. The aim of the present study was to investigate the efficacy of bis-pyridinium oximes on soman-inhibited neuromuscular transmission in muscle preparations from several species including man. The muscles tested were preparations of rat diaphragm and intercostal muscle, guinea-pig diaphragm, dog external intercostal muscle and human external intercostal muscle. These muscles were stimulated indirectly with field stimulation. With a few exceptions the preparations were exposed to soman for 2.5 or 15 min. In some cases different exposure times were employed or the organophosphate sarin was administered instead of its analogue soman. After the degree of inhibition of neuromuscular transmission had been established, oximes were added to the bath fluid. After washout 15 min later, recovery of neuromuscular transmission was tested. Subsequently, a second dose of soman was administered to investigate whether the recovery observed had been caused by cholinesterase reactivation. The results of these experiments indicate that the oximes tested, mostly HI-6, were quite effective as soman antidotes in muscle preparations of rats, guinea-pigs and dogs. In the human preparation while these oximes were quite effective after sarin intoxication they were essentially without effect against soman. Chemicals/CAS: 1 (3 carbamoylpyridinio) 1' (2 hydroxyiminomethylpyridinio)dimethyl ether, 22625-23-6; 1 (4 carbamoylpyridinio) 1' (2 hydroxyiminomethylpyridinio)dimethyl ether, 34433-31-3; sarin, 107-44-8; soman, 96-64-0; tubocurarine chloride, 57-94-3, 57-95-4, 8006-51-7; Antidotes; Chorionic Gonadotropin; HGG 52, 77704-19-9; HI 6, 34433-31-3; HS 6, 22625-23-6; Organophosphorus Compounds; Pralidoxime Compounds; Pyridinium Compounds; Sarin, 107-44-8; Soman, 96-64-0