Physiological, biochemical and histological changes due to physostigmine in monkeys.

Physostigmine (Phy), a short-acting reversible anticholinesterase agent is considered to be a potent prophylactic antidote for the highly toxic organophosphorous (OP) compounds. The toxic effects, if any, of the probable prophylactic doses of Phy have been evaluated by studying its physiological, biochemical and histological effects in monkeys. Phy only at 100 micrograms/kg resulted in certain cholinergic signs such as salivation, lacrymation and muscular faciculations; physiological changes such as mild tachycardia, tachypnea, higher amplitude in electrical activity of the brain, clinico-chemical effects like fall in PO2, PCO2 and alkalosis and histologically an inflammatory reaction in the lungs. On the other hand, the lower dose, i.e. 50 micrograms/kg appeared to be devoid of cholinergic signs and symptoms. However, we observed a significant inhibition of both plasma and erythrocyte ChE and increase in the rectal temperature in both the Phy treated groups. From this study, Phy at a dose of 50 micrograms/kg could be inferred as a safe, sign free intramuscular dose and may probably be used in pretreatment regimen against nerve agents.