Effects of a new phosphorothionate (RPR-V) on ATPases and acetylcholinesterase in rat brain by subchronic dosing.

The effect of a new phosphorothionate, the ethyl ester of 2-butenoic acid 3-diethoxy phosphinothioyl (RPR-V) synthesized at the Indian Institute of Chemical Technology, Hyderabad was studied using peroral doses of 0.033, 0.066 and 0.099 mg kg(-1) in male and female rats daily over 90 days. This repeated administration of RPR-V caused significant inhibition of acetylcholinesterase, Na+-K+, Mg2+ and Ca2+-ATPases in the brain of male and female rats when measured after 45 and 90 days of treatment. The effects of the low dose were generally not statistically significant, whereas medium and high doses caused significant effects. Females were more susceptible with regard to brain AChE, but the reverse was seen with Mg2+-ATPase, suggesting sexual dimorphism. Enzyme recoveries were seen 28 days after the final dose. Since RPR-V not only inhibited AChE but also ATPases, it is possible that both synaptic transmission and nerve conduction were affected.