Synthesis and adrenoreceptor blocking action of aziridinium ions derived from phenoxybenzamine and dibenamine

Article abstract of DOI:10.1021/jm00223a002

Crystalline perchlorate salts of aziridinium ions derived from phenoxybenzamine and dibenamine were prepared. Both aziridinium ions were tested on the rat vas deferens and found to possess α adrenergic potencies which were nearly identical with those of the parent compounds. The hydrolysis rates of phenoxybenzamine and dibenamine aziridinium ions in physiological medium were found to be 6.04 x 10^-4 and 8.35 x 10^-4 sec^-1, respectively. The rates of cyclization of the parent amines in aqueous medium were 1.9 x 10^-2 and 7.2 x 10^-3 sec^-1, respectively. The potencies and kinetic profiles indicate that the aziridinium ion is the only active species in α adrenergic blockade. Moreover, differences in potency between phenoxybenzamine and dibenamine appear to be exclusively to a difference in receptor affinity rather than to a difference in intrinsic alkylating ability.