Analysis of the mechanism of action of some ganglion-blocking drugs in the rabbit superior cervical ganglion.

1. Mechanisms of action of hexamethonium, mecamylamine and (+)-tubocurarine on the rabbit superior cervical ganglion were investigated by intracellular recording techniques.2. In concentrations up to 1 mM, none of these drugs affected the resting membrane potential nor altered the excitability of the postganglionic neurone to direct or antidromic stimulation.3. Post-tetanic potentiation of the excitatory postsynaptic potential (e.p.s.p.) was inhibited by mecamylamine (10-100 muM) but not affected by either hexamethonium (5-100 muM) or (+)-tubocurarine (10-50 muM).4. The decline in amplitude of successive e.p.s.ps in a train (40 Hz) was not influenced by hexamethonium or (+)-tubocurarine but was greatly exaggerated in the presence of mecamylamine; desensitization of the receptors for acetylcholine was excluded as a possible explanation for this latter finding.5. Mecamylamine depressed the quantal content of e.p.s.ps in a train, with the exception of the first e.p.s.p. which had an increased quantal content.6. Reduction in quantal content was attributed to a substantial fall in the size of the store of quanta of transmitter immediately available for release and to a reduction in the rate of mobilization of acetylcholine into that store; mecamylamine also caused a simultaneous increase in the fractional release.7. Hexamethonium and (+)-tubocurarine had no effect on transmitter release.8. The time-course of presynaptic effects of mecamylamine was similar to the duration of its postsynaptic blocking action.9. It is concluded that inhibition of ganglionic transmission by mecamylamine is due to both presynaptic and postsynaptic inhibitory actions; in contrast, hexamethonium and (+)-tubocurarine reduce transmission solely by their postsynaptic actions.