Selective blockade by nicergoline of vascular responses elicited by stimulation of alpha1A‐adrenoceptor subtype in the rat

The alpha 1 -adrenergic blocking activity of nicergoline was re-examined in rats, with a particular emphasis on alpha 1 -adrenoceptor subtypes. In pithed rats, nicergoline and prazosin infused at a single small dose (0.5 μg/kg/min i.v.) produced a substantial and identical shift to the right of the control dose pressor response curve to the specific alpha 1 -agonist cirazoline (ED 50 = 4.0 ± 0.1, 4.0 ± 0.1 and 0.9 ± 0.01 μg/kg i.v. for nicergoline, prazosin and vehicle respectively). In the isolated perfused mesenteric vascular bed, nicergoline strongly inhibited the pressor responses elicited by cirazoline, with approximately 40-fold higher potency (pA 2 = 11.1 ± 0.3) than prazosin (pA 2 = 9.5 ± 0.3). Conversely, nicergoline was 20-fold less potent than prazosin to antagonize the contractile effects of cirazoline in isolated endothelium-denuded aorta (pA 2 = 8.6 ± 0.2 and 9.9 ± 0.2 for nicergoline and prazosin respectively). Pretreatment of mesenteric vascular beds with chloroethylclonidine did not significantly modify nicergoline antagonistic potency (pA 2 = 10.6 ± 0.2). Nicergoline displaced [ 3 H]-prazosin bound to rat forebrain membranes pretreated with chloroethylclonidine (pK i = 9.9 ± 0.2) at concentrations 60-fold lower than in rat liver membranes (pK i = 8.1 ± 0.2). Finally, of the nicergoline metabolites studied, lumilysergol acted as a modest alpha 1 antagonist (bromonicotinic acid was devoid of alpha 1 antagonist activity). In conclusion, nicergoline is a potent and selective alpha 1A -adrenoceptor subtype antagonist, an alpha 1 -adrenoceptor subtype which is mainly represented in resistance arteries.