title: Relative contribution of alpha 1-adrenoceptor blocking activity to the hypotensive effect of the novel calcium antagonist monatepil.
abstract: Monatepil, a novel calcium antagonist, has alpha 1-adrenoceptor blocking activity; in the present study, we examined the relative contribution of this alpha 1-blocking activity to its hypotensive effect. Monatepil and diltiazem produced dose-dependent hypotensive effects in anesthetized rats with the same potency. Prazosin and monatepil inhibited the L-phenylephrine (L-PE)-induced pressor response, whereas diltiazem scarcely did. The injection of prazosin produced a decrease in blood pressure (BP) in anesthetized rats. The decrease was recovered with angiotensin II (AII) infusion in a dose-dependent manner. We developed a new rat model by first intravenously injecting prazosin and then infusing AII in anesthetized rats. In this model, diltiazem produced the same hypotensive effect as it did in pretreated conditions, although the hypotensive effect of monatepil was attenuated by 20-35% as compared with pretreated conditions. These results suggest that monatepil exerts alpha 1-adrenoceptor blocking action in vivo and 20-35% of the hypotensive effect of monatepil is attributed to its alpha 1-adrenoceptor blocking activity.
authors.affiliation: Department of Pharmacology, Dainippon Pharmaceutical, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
authors.forename: K
authors.initials: K
authors.lastname: Hosoki
authors.forename: T
authors.initials: T
authors.lastname: Karasawa
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003655:Decerebrate State; D003988:Dibenzothiepins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007022:Hypotension / Q000139:chemically induced; D007275:Injections, Intravenous; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011224:Prazosin / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D003988:Dibenzothiepins; D010879:Piperazines; D000804:Angiotensin II; D004110:Diltiazem; C067818:monatepil; D011224:Prazosin