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A single dose of guanethidine produces a substantial, long-lasting depletion of tissue catecholamines in the rat, whereas a similar dose of bretylium has no effect. Both drugs produce block of the eserine-induced sympathetic pressor effect. Block by guanethidine is induced more rapidly than is amine depletion. When amine depletion is maximal, a noradrenaline infusion is capable of restoring the response to eserine, but no restoration of the response to eserine occurs after noradrenaline infusion into bretylium-treated rats. Catecholamine levels in isolated tissues are not reduced when complete block of sympathetic nerve stimulation has been produced by guanethidine. It is suggested that guanethidine possesses a primary bretylium-like, and a secondary reserpine-like, blocking action. Guanethidine produces a transient lowering of intestinal 5-hydroxytryptamine, and this coincides with increased intestinal motility.
Cass et al. (Fri,) studied this question.