INTERACTIONS BETWEEN CALCIUM-CHANNEL BLOCKERS AND ALPHA-ADRENOCEPTORS IN THE HUMAN CORONARY AND MAMMARY ARTERIES - A RADIOLIGAND BINDING STUDY

1 The study was designed to assess whether Ca2+ channel blockers of the dihydropyridine family (felodipine, nicardipine, nifedipine, nimodipine, nitrendepine and nisoldipine), and of the phenylalkylamine family (verapamil) have any effect on alpha-adrenoceptor binding to sections of the human right coronary and mammary arteries, measured using [H-3]-dihydroergocryptine (DHT) as a ligand. 2 Increasing concentrations of nicardipine, verapamil and nitrendepine competed with [H-3]-DHT binding to sections of the human coronary and mammary arteries. The other compounds tested were without effect. Among the competitors of [H-3]-DHT binding, nicardipine was the most powerful, with a 50% inhibition (IC50) value of approximately 10 nM. 3 The pharmacological profile of competition with [H-3]-DHT binding by nicardipine, in the presence or in the absence of guanosine triphosphate and NaCl, is consistent with antagonist activity of the dihydropyridine derivative at the alpha-adrenoceptor. 4 This property may account for the lower sympathetic stimulatory activity elicited by nicardipine, in comparison with other Ca2+ channel blockers used in cardiovascular therapy.