PROTECTION AGAINST ALKYLPHOSPHATE INTOXICATION BY INTRACEREBRAL INJECTION OF 1-METHYL-2-FORMYLPYRIDINIUM IODIDE OXIME (2-PAM)

¹ Department of Pharmacology and Toxicology, The University of Wisconsin Medical School, Madison, Wisconsin

Prophylactic protection by intraperitoneally administered l-methyl-2-formylpyridinium iodide oxime (2-PAM) against tetraethylpyrophosphate, paraoxon and diisopropyl phosphorofluoridate intoxication in mice was markedly enhanced by intracerebral administration of this antagonist into the central nervous system.

Potency ratios and LD50 values of these alkylphosphates were compared in groups of mice premedicated with 2-PAM and/or atropine. The 2-PAM was administered by the intraperitoneal, intracerebral, and combined intracerebral-intraperitoneal route.

These results indicated that the intracerebral administration of 2-PAM alone had little or no effect in antagonizing these alkylphosphates. Although some protection was afforded by 2-PAM intraperitoneally, its effects were markedly enhanced by combined administration of 2-PAM by the intracerebral-intraperitoneal routes. These effects were even more striking when tested in combination with atropine sulfate. The most effective protection against alkylphosphate intoxication was obtained by intracerebral-intraperitoneal administration of 2-PAM in combination with atropine intraperitoneally. Mechanisms for this potentiation of the efficacy of 2-PAM against alkylphosphate intoxication were discussed.