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

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Abstract
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 μm) but not affected by either hexamethonium (5–100 μm) or (+)-tubocurarine (10–50 μm). 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.