Effect of sympathomimetic amines on the blocking action of guanethidine, bretylium and xylocholine.

Experiments were carried out in which the adrenergic neurone blocking activity of xylocholine, bretylium and guanethidine was studied by the use of the inhibitory responses of the isolated rabbit ileum to lumbar sympathetic nerve stimulation, and the contractions of the nictitating membrane of the anaesthetized cat in response to stimulation of the cervical sympathetic nerves. In both these preparations, after blockade of the effects of sympathetic nerve stimulation had been produced with xylocholine, bretylium or guanethicdine, the sympathomimetic amines, dexamphetamine, mephentermine, hydroxyamphetamine, ephedrine and phenethylamine, reversed the blockade; if these amines were given first, then the adrenergic neurone blocking agents were ineffective. Tyramine and dopamine were effective on the isolated rabbit ileum but not on the cat's nictitating membrane. Effective antagonism of the adrenergic neurone blocking drugs was also shown by some substances which inhibit mono-amine oxidase but only those which in addition possess sympathomimetic effects. Thus phenelzine, pheniprazine and tranylcypromine were effective whereas iproniazid and nialamide were not. Since xylocholine, bretylium and guanethidine were all antagonized by the same agents, it seems likely that they all produce sympathetic blockade by a similar mechanism. The possibility is discussed that the sympathomimetic amines which antagonize the adrenergic neurone blocking drugs are competing with these substances for the same receptor sites.