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.
Ichihara
K
K
Department of Pharmacology, Maruko Pharmaceutical Co., Ltd., Kasugai, Japan.
Okumura
K
K
Mori
H
H
Nagasaka
M
M
D000284:Administration, Oral; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D000068438:Brimonidine Tartrate; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D003655:Decerebrate State; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004558:Electric Stimulation; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D000068438:Brimonidine Tartrate; C059427:aranidipine; D009543:Nifedipine; D009638:Norepinephrine