Br Frost

The indirect sympathomimetic activity of etilefrine — a comparison with tyramine and ephedrine using [3H]noradrenaline

The indirect sympathomimetic activity of etilefrine has been examined using the ventral caudal artery of the rat. This vessel has a rich sympathetic innervation and lends itself to studies on [3H]noradrenaline efflux from these sites. Etilefrine possessed significant indirect activity on the artery and this action, although less than that of tyramine, was equivalent to that caused by ephedrine. Pretreatment of the vessels with a mixture of iproniazid, doca, cocaine and U0521 (3′,4′‐dihydroxy‐2‐methyl propiophenone) significantly enhanced[3H]‐noradrenaline efflux from the artery.

The effects of etilefrine on blood vessels in the rat tail.

Etilefrine was found to constrict blood vessels in the rat tail through a mechanism which was partly dependent on the sympathetic nerves present in these vessels. The response to the drug was enhanced by pretreatment with noradrenaline and cocaine, and totally abolished by the α‐receptor antagonist phentolamine. When compared with several other sympathomimetic agents which were tested on the vessel, etilefrine appeared to have a low order of vasoconstrictor activity. These findings would seem to have considerable relevance to the clinical situation where an attempt has been made to use etilefrine in the treatment of patients with orthostatic hypotension.

The effect of sympathomimetic agents on noradrenaline efflux from a blood vessel

The effect of several sympathomimetic agents on the efflux of noradrenaline and its metabolites has been evaluated using the ventral artery of the rat tail as the experimental model. This vessel is richly endowed with sympathetic nerves and is therefore well suited to examine the efflux patterns of that transmitter. Etilefrine, tyramine, ephedrine and REN-293 were all found to increase the efflux of 3H-noradrenaline and/or 3H-DOPEG to different degrees from the artery. Possible reasons for this variation in metabolite efflux are discussed.

The effect of local anaesthetics on the vasoconstrictor response of the isolated perfused artery to adrenaline and noradrenaline

The vascular response to intraluminally and extraluminally administered catecholamines mixed in combination with local anaesthetics has been studied using the isolated perfused rabbit ear artery as the model system. Potentiation of the vascular response to extraluminal adrenaline was observed when prilocaine, lignocaine or cocaine were combined in low concentrations with the vasoconstrictor. No potentiation of the vascular response to extraluminally administered noradrenaline could be demonstrated in the presence of prilocaine or lignocaine. Further, no potentiation to either catecholamine was found if the artery had been denervated or the drugs were applied intraluminally. Possible mechanisms for the potentiation of extraluminally applied adrenaline are discussed.