THE PHYSIOLOGICAL AND PHARMACOLOGICAL ROLE OF PRESYNAPTIC ALPHA-ADRENOCEPTORS AND BETA-ADRENOCEPTORS IN MAN

1 Two studies were performed each in six normal volunteers in order to find evidence of either a physiological or pharmacological role of presynaptic .alpha.- and presynaptic .beta.-adrenoceptors in man. 2 In study 1 subjects received a 60 min infusion of guanfacine 3 mg (.alpha.2-adrenoceptor agonist) preceded by either idazoxan (.alpha.2-adrenoceptor antagonist) or vehicle. 3 Guanfacine reduced plasma noradrenaline concentration by approximately 30% and this fall was not antagonized by the .alpha.2-receptor antagonist. The 30-fold increase in plasma growth hormone, measured as a marker of the central action of guanfacine, was almost completely blocked by idazoxan. 4 A comparison of the drug concentrations of idazoxan and guanfacine, together with their relative affinities for .alpha.2-adrenoceptors, suggested that the idazoxan could not block the peripheral actions of guanfacine and that these were responsible for the fall in plasma noradrenaline concentration. 5 In Study 2 adrenaline 0.05 .mu.g kg-1 min-1 was infused for 80 min preceded by either idazoxan or vehicle. 6 After vehicle, adrenaline caused no change in plasma noradrenaline concentration whereas it rose approximately 25% after administration of idazoxan. This was probably due to unmasking of presynaptic .beta.-adrenoceptor stimulation by adrenaline when the opposing inhibitory autoreceptor was blocked.