E. Hodgson, J. Casida
Sep 1, 1961
Citations
0
Influential Citations
80
Citations
Quality indicators
Journal
Biochemical pharmacology
Abstract
Abstract N:N-Dimethyl- p -nitrophenyl carbamate is metabolized by an enzyme or enzyme system of rat liver microsomes which requires TPNH and oxygen. The resulting product can be extracted into organic solvents and decomposes in strong acid to yield formaldehyde. Its stability in alkali is intermediate between that of the substrate and N-methyl- p -nitrophenylcarbamate. It is formed in vivo by rats and probably by certain insects. The rate at which this or similar systems, in vitro , will attack analogs of N:N-dimethyl- p -nitrophenyl carbamate with different alkyl groups is considerably reduced when the alkyl groups are longer than ethyl. These enzyme systems are inhibited by β-diethylaminoethyl diphenylpropyl acetate (SKF 525-A), by the methylene dioxyphenyl compounds, piperonyl butoxide and sesamex, and by N-octyl bi cyclo heptane dicarboximide. The metabolism of twenty-five N:N-dimethyl carbamates and twenty-three related compounds was investigated. Isolan metabolism was evident when followed both by the formation of formaldehyde-yielding material and reduction in the ability to inhibit cholinesterase in vitro . Metabolism of certain other carbamates gave formaldehyde-yielding materials without loss in cholinesterase-inhibiting activity.