Inhibition of adrenergic neurotransmission by clonidine: An action on prejunctional α-receptors

Abstract

According to previous work, several sympathomimetic agents decrease the release of noradrenaline in response to nerve impulses by an action on α-receptors which may be localized prejunctionally. The possibility of a similar mechanism of action of the antihypertensive agent clonidine was investigated in isolated rabbit hearts with intact postganglionic sympathetic nerves. (1) Clonidine diminished the overflow of noradrenaline evoked by sympathetic nerve stimulation. The degree of this inhibition was inversely related to the overflow caused by the control stimulation period before the infusion of clonidine. The negative correlation presumably reflects the competition between clonidine and liberated noradrenaline for a common inhibitory mechanism. (2) Clonidine prevented the increase of the stimulation-induced overflow of noradrenaline caused by phentolamine, but not that caused by cocaine. (3) The inhibition caused by both clonidine and the α-receptor-stimulant drug oxymetazoline was abolished by preinfusion of phenoxybenzamine. It is concluded that clonidine shares with other sympathomimetic agents the ability to depress the liberation of noradrenaline by an action on-probably prejunctional-α-receptors. The significance of this finding for the central hypotensive effect of clonidine is discussed. © 1973.