NONEQUILIBRIUM ALPHA ADRENERGIC BLOCKADE AND NEUROLEPTIC ACTIVITY OF N-ETHOXYCARBONYL-1,2-DIHYDROQUTNOLINE (BC-347)

¹ Bristol Laboratories of Canada, Limited, Candiac, Quebec, Canada

N-ethoxycarbonyl-1, 2-dihydroquinoline (BC-347), a member of a novel class of compounds studied in our laboratories, has been found to produce alpha adrenergic inhibition and marked depression of the central nervous system. The blockade produced was specific, complete and persistent and could not be reversed by large concentrations of epinephrine. This implies that mass-action equilibration between agonist and antagonist is prevented (nonequilibrium blockade). Until now, this type of adrenergic blockade has been reported only with compounds having the ability to form stable covalent bonds at the receptor site (Dibenamine and its relatives). From a chemical viewpoint, BC-347 does not appear to be reactive enough to form such a covalent linkage. This suggests that BC-347 may be transformed before acting at the alpha receptor level. The central nervous system depression produced is analogous to that of the neuroleptics and is characterized by a progressive decrease in activity, inhibition of conditioned response and cataleptic behavior. The pharmacologic profile of BC-347 is unique since it combines nonequilibrium alpha adrenergic blockade with neuroleptic activity. Haloalkylamines (Dibenamine and its relatives), the only other series of compounds producing irreversible alpha blockade, do not produce central nervous system depression.