SIMULTANEOUS COMPARISON OF NICOTINIC RECEPTOR ANTAGONISTS ON 3 NICOTINIC ACETYLCHOLINE-RECEPTORS

The relative potencies of several nicotinic cholinoceptor antagonists in producing tetanic fade and reduction of striated muscle contraction were investigated in the isolated guinea-pig oesophagus as well as th e guinea-pig and rat phrenic nerve-diaphragm preparations. Contractile smooth muscle responses to vagal stimulation, which involves ganglion ic activation, were also measured simultaneously with striated muscle responses in the oesophagus. The relative potency for inhibiting the r esponse of oesophageal smooth muscle to vagal stimulation (20 Hz) was trimetaphan > mecamylamine > hexamethonium > tubocurarine > pancuroniu m. For oesophageal striated muscle, production of tetanic fade at 100 Hz and reduction in peak tetanic tension at 20 or 100 Hz showed a simi lar relative potency; pancuronium > tubocurarine > mecamylamine > trim etaphan > hexamethonium and similar results were obtained in the guine a-pig diaphragm for the antagonists investigated (pancuronium, tubocur arine and mecamylamine). In the rat phrenic nerve-diaphragm preparatio n, production of tetanic fade at 50 Hz and reduction in twitch or teta nic tension all showed the relative potency; tubocurarine > pancuroniu m > mecamylamine > trimetaphan > hexamethonium. These findings indicat e differences in the nicotinic cholinoceptor subtypes involved in vaga l ganglionic responses and those in tetanic fade.