Therapy of organophosphate poisoning: the marmoset as a model for man

Abstract

1 The ability of various bis-pyridinium oximes to restore organophosphate-inhibited neuromuscular transmission in vitro was compared in human intercostal and marmoset diaphragm muscles. 2 HI-6 (2-hydroxyiminomethyl-pyridinium-1-methyl-4'-carbamoyl-pyridinium-1'-methyl ether dichloride monohydrate) appeared very effective against VX (O-ethyl S-2-diisopropylaminoethyl methylphosphonothioate) and sarin in both muscles, whereas obidoxim was quite effective against tabun. 3 Against soman, HI-6, HS-6 (2-hydroxyiminomethyl-pyridinium-1-methyl-3'-carbamoyl-pyridinium-1'-methyl ether dichloride dihydrate) and obidoxim had little effect in the human muscle and only slight activity in the marmoset muscle; HGG-12 (2-hydroxyiminomethyl-pyridinium-1-methyl-3'-phenylcarbonyl-pyridinium-1'-methy l ether dichloride) and benzyl-P2A (1-benzyl-2-hydroxyiminomethyl-pyridinium methanesulphonate) were ineffective. 4 Anaesthetized, atropinized marmosets were poisoned with soman (4 X LD50, i.v.) and subsequently treated with HI-6, HS-6 or HGG-12. Only HI-6 and HS-6 were marginally effective in restoring respiration and neuromuscular transmission. 5 Marmoset muscle is a reasonable model for human muscle for the study of organophosphate poisoning and therapy.