The conversion of dimefox into an anticholinesterase by rat liver in vitro

Abstract

Dimefox is a weak anticholinester-ase, and its effect on rat-erythrocyte cholinesterase may be reversed by washing the intact cells. Dimefox is converted into a powerful and unstable anticholinesterase in liver tissue. A technique for investigating the system in vitro is described. The stability of the metabolite is further decreased by the presence in liver, blood and kidney of a substance which inactivates it. The converting system is present in the microsomes and soluble material of the liver cells, and bears certain resemblances to the system which metabolizes barbiturates and other drugs. It is probably the same as that which activates schradan. The conversion in liver suspensions is accelerated by DPN and nicotinamide, and by Ca2+ or Mg2+ ions. It is inhibited in liver slices by lack of oxygen, by barbiturates, SKF 525-A (2-(diethylamino)) ethyl diphenylpropylacetate hydrochloride), 2:4-dinitrophenol and potassium cyanide. No site of conversion of dimefox in the rat other than liver could be demonstrated in vitro. Conversion of dimefox also takes place in whole cockroach gut in vitro, but homogenates fortified with DPN, nicotinamide and Mg were inactive.