INHIBITION OF RAT BRAIN CHOLINESTERASE BY ß-CHLORINATED AMINES

Abstract

A study was undertaken of the inhibition of the cholinesterase system of rat brain by excess substrate, a series, of beta-chlorinated amines, and some other convulsant and anticonvulsant drugs. The enzyme was shown to combine with 2 moles of acetylcholine to form an inactive complex with a dissociation constant of 1.6 x 10-2 [image]. The structure necessary for inhibitory activity by the beta-chlorinated amines was elucidated and shown to correlate with that necessary for convulsant activity, in both cases the minimum necessary structure for activity being CH3N(C2H4C1)2 or CH3N(C2H5) C2H3Cl2. Strychnine and nicotine were inhibitors of cholinesterase, but metrazol and picrotoxin were not. The anticonvulsants, phenobarbital, trimethadione, phenacetylurea, diphenylhydantoin, and atropine, had no effect on the enzyme, nor did they reverse the effect of any of the inhibitors studied. Inhibition of the enzyme by the beta-chlorinated amines was reversed by cysteine. The results are discussed with regard to the mechanism of action of convulsant drugs.