Antagonism of pro-2-PAM using central and peripheral anticholinergic drugs

Abstract

The goal of this study was two-fold. Experiment 1 characterized the intoxicating tremor produced by two known tremor-inducing drugs, oxotremorine and physostigmine in order to characterize the tremoregenic effects of a centrally acting oxime, pro-2-PAM. Pro-2-PAM crosses the blood brain barrier and may have therapeutic value against OP intoxication. Experiment 2 attempted to antagonize the tremor produced by 28.0 mg/kg of pro-2-PAM with a Med Associates System using central and peripheral anticholinergics. The centrally acting anticholinergics were atropine sulfate and scopolamine HBr; the peripherally acting anticholinergics were AMN and SMN. In Experiment 1, the only drugs that showed a tremoregenic effect against their controls were oxotremorine and physostigmine. A high dose of physostigmine (0.4 mg/kg) induced more tremor than 0.1 mg/kg of oxotremorine; only 0.1 mg/kg of oxotremorine induced more tremor than 28.0 mg/kg of pro-2-PAM. In Experiment 2, only the centrally acting anticholinergics reduced the tremoregenic effect of pro-2-PAM.