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

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Abstract
The ability of various bis‐pyridinium oximes to restore organophosphate‐inhibited neuromuscular transmission in vitro was compared in human intercostal and marmoset diaphragm muscles. 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. Against soman, HI‐6, HS‐6 (2‐hydroxyiminomethyl‐pyridinium‐1‐methyl‐3′‐ carbamoylpyridinium‐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′‐methyl ether dichloride) and benzyl‐P2A (1‐benzyl‐2‐hydroxyiminomethyl‐pyridinium methanesulphonate) were ineffective. Anaesthetized, atropinized marmosets were poisoned with soman (4 × 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. Marmoset muscle is a reasonable model for human muscle for the study of organophosphate poisoning and therapy.