A New Selective Antagonist of Vascular Serotonin Receptors Lowers Blood Pressure in Spontaneously Hypertensive Rats

Several data support the involvement of serotonin (S-HT) in the pathogenesis of hypertension (Vanhoutte 1985). Therefore in recent years the selective antagonism of vascular serotonin receptors has been pursued as a target for a new class of antihypertensive agents. Ketanserin was the first serotonergic-receptor antagonist shown to be active in lowering blood pressure in man; however, it is now recognised that its concomitant Q!,-adrenoreceptor blocking activity contributes to its antihypertensive effect (De Cree et al. 1981; Fozard 1982). The aim of the present work is to describe the pharmacological profile of an ergoline derivative, FCE 24379 (l-[S( 1O-9)abeo-6-methyl-9, lO-didehydro-ergolin-8{j-methyl]dihydrouracyl), which is highly selective in antagonising vascular serotonergic receptors in isolated arterial vessels and also iowers blood pressure in spontaneously hypertensive rats (SHR).