title: Antihypertensive properties of the novel calcium antagonist (1S,2S)-2-[2-[[3-(2-benzimidazolyl)propyl]methylamino] ethyl]-6- fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphthyl methoxyacetate dihydrochloride in rat models of hypertension. Comparison with verapamil.
abstract: (1S,2S)-2-[2-[[3-(2-Benzimidazolyl)propyl]methylamino]ethyl]-6- fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphthyl methoxyacetate dihydrochloride (Ro 40-5967) is a novel calcium antagonist. Its effect on systolic arterial blood pressure and heart rate was investigated in comparison with verapamil in conscious spontaneously hypertensive rats (SHR), renal hypertensive rats (2K1C), deoxycorticosterone acetate (DOCA)-NaCl hypertensive rats and normotensive Wistar rats. After single oral doses, Ro 40-5967 (3-30 mg/kg) and verapamil (10-100 mg/kg) produced a dose-related decrease in blood pressure in all three types of hypertensive rats. Ro 40-5967 was 3-5 times more potent than verapamil. DOCA-NaCl hypertensive rats were more sensitive to the antihypertensive action of Ro 40-5967 than renal hypertensive rats and SHR. Both compounds lowered blood pressure of normotensive rats to a lesser degree than that of hypertensive rats. The antihypertensive effects of Ro 40-5967 and verapamil occurred fast, with similar efficacies and reached maximal values 3 and 6 h postdrug (SHR). While the significant antihypertensive effect of Ro 40-5967 (30 mg/kg) persisted for 24 h, that of verapamil (100 mg/kg) recovered completely 16 h postdrug. The experimental data suggest that Ro 40-5967 might be suitable for clinical use as a once-a-day antihypertensive agent.
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Hefti
authors.forename: J P
authors.initials: JP
authors.lastname: Clozel
authors.forename: W
authors.initials: W
authors.lastname: Osterrieder
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents; D001562:Benzimidazoles / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003900:Desoxycorticosterone; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D020748:Mibefradil; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D020748:Mibefradil; D003900:Desoxycorticosterone; D014700:Verapamil