The conversion of methyl-2-acetoxyethyl-2'-chloroethylamine to an acetylcholine-like aziridinium ion and its action on the isolated guinea pig ileum.

Methyl-2-acetoxyethyl-2′-chloroethylamine (acetyicholine-mustard) isomerizes in aqueous solution to form a cyclic ion, N-methyl-N-(2-acetoxyethyl)aziridinium, which structurally resembles acetylcholine. It is a potent stimulant of the guinea pig ileum, being approximately one-sixth as potent as acetylcholine at pH 7.4 and one-third as potent at pH 8.4. The agonist activity is inhibited by atropine, by preincubation with acetylcholinesterase, and pretreatment with thiosulfate ion. Mepyramine does not inhibit the stimulant action.One hour exposures of ileum segments to concentrations of acetylcholine-mustard in excess of those producing maximal responses, followed by a 1 h recovery period, did not produce evidence of postsynaptic receptor alkylation. Post-treatment responses to acetylcholine were slightly depressed, but these reductions were not related to the incubation concentrations of the agonist haloalkylamine. Pilocarpine-induced responses were unaltered by this treatment whereas 5-hydroxytryptamine r...