ANALYSIS OF MODE OF ACTION OF SOME NICOTINIC BLOCKING DRUGS

Hexamethonium and tetraethylammonium (TEA) produced parallel shifts (equilibrium blockade) of nicotine and dimethylphenylpiperazinium dose-response curves at all dose levels on isolated rabbit and guinea pig ileum preparations, while mecamylamine, pempidine, chlorisondamine and pentolinium produced parallel shifts at lower doses and nonparallel shifts (nonequilibrium blockade) at higher dose levels. Hexamethonium and TEA protected against the nonequilibrium blockade by mecamylamine, pempidine, chlorisondamine and pentolinium. Dose ratios for the combination of hexamethonium with TEA, with chlorisondamine or with pentolinium were consistent with competitive type of blockade. Dose ratios for the combination of hexamethonium with mecamylamine or with pempidine were not consistent with the noncompetitive type of blockade. It is concluded, that hexamethonium and TEA act as equilibrium competitive ganglion blockers while mecamylamine, pempidine, chlorisondamine and pentolinium act as nonequilibrium competitive ganglion blockers.