THE ACTIONS OF BRETYLIUM - ADRENERGIC-NEURON BLOCKING AND OTHER EFFECTS (REPRINTED FROM BRIT J PHARMACOL, VOL 14, PG 536, 1959)

Bretylium caused a specific and lasting depression of many excitatory and inhibitory responses evoked by electrical stimulation of the perip heral sympathetic nervous system, probably by impairing conduction of impulses in adrenergic neurones with consequent failure of noradrenali ne and adrenaline release. This effect, which will be referred to as t he adrenergic neurone blocking action, was preceded by weak sympathomi metic effects. In the presence of bretylium the effects of adrenaline and noradrenaline were increased, as after sympathectomy. Concentratio ns producing blocking of adrenergic neurones did not prevent the relea se of adrenaline and noradrenaline from the adrenal medulla by splanch nic nerve stimulation or by the injection of dimethylphenylpiperaziniu m iodide, nor did they cause antiparasympathetic or parasympathomimeti c effects. No action on the central nervous system has been detected. Curare-like neuromuscular block occurred with 10 to 30 times the amoun t required 20 block the response to adrenergic nerve stimulation alone and was accompanied by signs of temporary synaptic block in autonomic ganglia. Adrenegic nerve trunks and sensory nerves in the skin were r eadily blocked for long periods by topical application of bretylium, w hereas the phrenic nerve of the rat was not. Bretylium had little effe ct on gastrointestinal propulsion or on the sensitivity of smooth musc le to acetylcholine, 5-hydroxytryptamine, adrenaline, or noradrenaline , but moderate amounts depressed the peristaltic reflex and the sensit ivity of the guinea-pig ileum to histamine. Bretylium caused postural hypotension in the cat in doses which had little effect on the supine blood pressure. Experiments on the nictitating membrane indicated that compensation for the effects of bretylium on low rates of stimulation of postganglionic sympathetic nerves could be attained by a small inc rease in the rate of stimulation, whereas compensation for its effects on high rates required an increase in the rate of stimulation beyond physiological limits.