Effects of MPC-1304, a novel Ca2+ entry blocker, on alpha-adrenoceptor-mediated pressor responses in pithed rats

MPC-1304 is a novel Ca2+ entry blocker of the 1,4-dihydropyridine type. In the present study, the effect of oral administration of MPC-1304 on alpha-adrenoceptor-mediated pressor responses was examined in pithed rats and compared with that of nifedipine. Drugs were administered orally to conscious animals before pithing. MPC-1304 (0.3-3 mg/kg) and nifedipine (1-10 mg/kg) inhibited pressor responses to norepinephrine, phenylephrine (alpha 1-adrenoceptor agonist), UK-14304 (alpha 2-adrenoceptor agonist), and sympathetic nerve (spinal cord segments) stimulation. MPC-1304 was roughly 3 times more potent than nifedipine in inhibiting these responses. The inhibitory effect of MPC-1304 (3 mg/kg) on the pressor response to UK-14304 lasted longer than that of nifedipine (3 mg/kg). At the same time, plasma concentrations of MPC-1304 were lower than those of nifedipine. These results suggest that MPC-1304 has a great ability to inhibit pressor responses to norepinephrine and peripheral sympathetic stimulation after its oral administration, and that this effect of MPC-1304 is closely correlated with its potent antihypertensive activity.