US EPA

1620471 

Journal Article 

Dual mechanism of the antidotal action of atropine-like drugs in poisoning by organophosphorus anticholinesterases 

Green, DM; Muir, AW; Stratton, JA; Inch, TD 

1977 

Yes 

Journal of Pharmacy and Pharmacology
ISSN: 0022-3573 

HEEP/78/10126 

29 

1 

62-64 

HEEP COPYRIGHT: BIOL ABS. Some atropine-like drugs are shown to have anticonvulsant action which may contribute to their ability to counteract the effects of poisoning by high doses of anticholinesterases (from chemical warfare agents and pesticides). The central and peripheral antimuscarinic activities of atropine and 5 related drugs in mice, together with a measure of their abilities, when used with an oxime, to protect rats against poisoning by isopropyl methylphosphonofluoridate (Sarin) are given. Relations between protection and the administered dose of the atropine-like drugs are summarized. The drugs were: atropine sulfate, N-methyl piperidin-4-yl phenyl-cyclopentane carboxylate hydrochloride (G3063), N-ethyl pyrollidine-2-phenylacetate hydrochloride, hyoscine hydro-bromide, N-methyl-piperidin-4-yl(S+)-2-cyclohexyl-2-hydroxy-2-phenylacetate hydrochloride, N-methyl-piperidin-4-yl(R-)-2-cyclohexyl-2-hydroxy-2-phenylacetate hydrochloride. The protection afforded by atropine-like drugs against low dosages of organophosphorus anticholinesterases is related to their antimuscarinin activity whereas the anticonvulsant properties of atropin-like drugs become important for protection against higher dosages of anticholinesterases. In man, where only lower doses of antimuscarinic drugs are usually administered, it is the antimuscarinic properties that are most important. There is no direct evidence presently to show that the convulsive mechanisms which are operative in the anticonvulsant tests on which this hypothesis is partly based are similar to the convulsive mechanisms which result from poisoning by anticholinesterases.