The chronic administration of O,O-diethyl S-2-(ethylthio)ethyl phosphorodithioate (Di-Syston) is accompanied by the development of tolerance to the cholinomimetic effects of this compound. Rats which had developed tolerance to Di-Syston were found to be less susceptible to the subacute lethal action of octamethyl pyrophosphoramide (OMPA) than control rats. The sensitivity of Di-Syston-tolerant rats to the subacute lethal action of parathion, however, was unchanged. Di-Syston tolerant rats were also found to be resistant to the acute lethal action of oxotremorine, but the sensitivity of these rats to the acute lethal action of d-tubocurarine, decamethonium, and OMPA was increased. The chronic administration of Di-Syston appears to produce some type of change in rats which reduces susceptibility to certain cholinomimetic drugs. The results with d-tubocurarine and decamethonium would suggest that, at the same time, the susceptibility to neuromuscular blocking drugs is increased. © 1969.
