In vitro pharmacologic profile of Ro 40-5967, a novel Ca2+ channel blocker with potent vasodilator but weak inotropic action.
Ro 40-5967 is a structurally novel Ca2+ channel blocker which binds to the verapamil-type receptor of cardiac membranes. Its biological activity was investigated in comparison with verapamil in isolated vascular, cardiac, and gastrointestinal muscle preparations, as well as in isolated perfused hearts. Ro 40-5967 was more potent in increasing coronary artery flow (EC50 = 54 nM) than in suppressing myocardial (IC50 = 14,000 nM) and peripheral vascular (aortic) contractility half-maximal inhibition (IC50 = 275 nM). In contrast, verapamil was equally potent in affecting all three variables. These observations demonstrate an apparent preference of Ro 40-5967 for the coronary vasculature, as opposed to verapamil, in vitro. Results also suggest that Ro 40-5967 is less potent than verapamil in gastrointestinal smooth muscle.
Osterrieder
W
W
Pharmaceutical Research Department, F. Hoffmann-La Roche, Basle, Switzerland.
Holck
M
M
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D020748:Mibefradil; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D014665:Vasodilator Agents; D020748:Mibefradil; C043184:4-desmethoxyverapamil; D014700:Verapamil