Transdermal patch containing physostigmine and procyclidine protects rhesus monkeys against VX intoxication

Abstract

ABSTRACTVX is an organophosphate cholinesterase inhibitor known as a chemical warfare agent. This study was designed 1) to determine the acute toxicity of VX in male rhesus monkeys by subcutaneous administration, 2) to evaluate the efficacy of a transdermal patch containing physostigmine and procyclidine. The median lethal dose (LD50) of the subcutaneous injection of VX was 15.409 ug/kg, which was calculated using the up-and-down dose selection procedure based on deaths occurring within 48 h. To test the efficacy of the transdermal patch, rhesus monkeys were treated with a patch (5×5 cm2) alone or in combination with post-exposure therapy comprising atropine plus 2-pralidoxime (2-PAM), and then administered subcutaneous injection of VX at various doses. The rhesus monkeys pretreated with the patch alone were 100% protected against 1.5×LD50 of VX, while the rhesus monkeys treated with the patch, atropine, and 2-PAM were 100% protected against 50×LD50 of VX. This study demonstrated that patch pretreatment in conjunction with atropine and 2-PAM treatment is an effective regimen against high doses of VX.