Hemodynamic profile of Ro 40-5967 in conscious rats: comparison with diltiazem, verapamil, and amlodipine.
Ro 40-5967 is a new calcium antagonist that binds to the same site as verapamil but that has been shown to have a much lesser negative inotropic effect than verapamil. The goal of the present study was to assess the hemodynamic profile of Ro 40-5967 not only in comparison with verapamil but also with diltiazem and amlodipine. For this purpose, hemodynamic parameters were assessed in conscious normotensive rats by measuring mean arterial pressure (MAP), left ventricular (LV) dP/dtmax, and heart rate. Dose-response curves were obtained with intravenous injection of the four drugs. Despite similar decreases in arterial pressure, the effects of the four drugs on left ventricular contractility and heart rate were different. Verapamil and diltiazem were markedly negative inotropic. Amlodipine decreased left ventricular contractility only at the highest dose. Ro 40-5967 was less negative inotropic than amlodipine. Verapamil, diltiazem, and Ro 40-5967 did not alter heart rate or slightly decreased it. In contrast, amlodipine induced a reflex tachycardia. In conclusion, because of its very low negative inotropism and its lack of reflex tachycardia, Ro 40-5967 seems to have a unique hemodynamic profile among calcium antagonists.
Véniant
M
M
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Clozel
J P
JP
Hess
P
P
Wolfgang
R
R
D017311:Amlodipine; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D020748:Mibefradil; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D013764:Tetrahydronaphthalenes; D017311:Amlodipine; D020748:Mibefradil; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine