Potential-dependent inhibition of cardiac Ca2+ inward currents by Ro 40-5967 and verapamil: relation to negative inotropy.
Ro 40-5967 is a structurally novel Ca2+ channel blocker which binds to the [3H]desmethoxyverapamil receptor in cardiac membranes with a potency similar to that of verapamil but which has considerably fewer negative inotropic effects. In the present study, the inward Ca2+ current was measured in isolated myocytes with the whole-cell patch-clamp technique. It was found that at a physiological membrane potential (-80 mV) Ro 40-5967 was also less potent than verapamil in inhibiting this current, and that negative inotropy and Ca2+ channel blockade were correlated.
Fang
L M
LM
Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Osterrieder
W
W
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D003864:Depression, Chemical; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials; D020748:Mibefradil; D009200:Myocardial Contraction / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013764:Tetrahydronaphthalenes; D020748:Mibefradil; D014700:Verapamil