Ro 40-5967, in contrast to diltiazem, does not reduce left ventricular contractility in rats with chronic myocardial infarction.
Ro 40-5967 is a new calcium antagonist that binds to the same binding 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 compare the effects of Ro 40-5967 and diltiazem on left ventricular contractility in vitro and in vivo in normal rats and in rats with chronic myocardial infarction induced by ligating the left coronary artery. Left ventricular contractility was assessed in vitro in isolated perfused hearts and in vivo in conscious rats by measuring left ventricular dP/dtmax + and dP/dt at P 40. In vitro, both Ro 40-5967 and diltiazem did not decrease cardiac contractility up to a dose producing complete atrioventricular block. In vivo, diltiazem decreased dP/dtmax + and dP/dt at P 40. Ro 40-5967 was less negative inotropic than diltiazem. We conclude that if these results were confirmed in clinical trials. Ro 40-5967 might be a safer drug than diltiazem, especially in patients with left ventricular dysfunction.
Véniant
M
M
Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Clozel
J P
JP
Hess
P
P
Wolfgang
R
R
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003864:Depression, Chemical; D004110:Diltiazem / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D020748:Mibefradil; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D013764:Tetrahydronaphthalenes; D020748:Mibefradil; D004110:Diltiazem