Inotropic and electrophysiological actions of verapamil and D 600 in mammalian myocardium. II. Pattern of inotropic effects of the optical isomers.
On isotonically contracting cat papillary muscles analysis, a comparison of the effects of the optical isomers of verapamil and D 600 and the racemic drugs was performed. 1. (-)-verapamil (0.2-3.0 mug/mo) and (-)-D-600 (0.1 mug/ml-3.0 mug/ml) leave the steady state contraction amplitudes nearly unchanged at 6/min, but produce a strong depression at 60/min. (-)-D 600 is about 8 times as effective as (-)-verapamil. The (+)-isomers exert only a moderate negative inotropic effect (particularly at low frequencies). 2. Increase of [Ca2+]O does not restitute the normal amplitude-frequency relationship during exposure to either the (-)-isomers or the (+)-isomers. 3. The (-)-isomers lead to typical biphasic staircases after step changes of frequency. A fast negative staircase occurs first followed by a rather slowly developing positive staircase. In contrast, the (+)-isomers have little influence on the usual staircase pattern. 4. The strength-interval relationship for single test contractions elicited after frequent conditioning stimulation indicated that the (-)-isomers probably slow the restitution of intracellular Ca-reavailability. The (+)-isomers have no such effects. 5. The effects produced by the (+/-)-compounds correspond qualitatively to those of the (-)-isomers. 6. The very different patterns of inotropic actions observed indicate that the (-)- and (+)-isomers of verapamil and D 600 probably interfere with cardiac excitation-contraction coupling at different sites.
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002415:Cats; D003864:Depression, Chemical; D004558:Electric Stimulation; D005711:Gallopamil / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009904:Optical Rotation; D013237:Stereoisomerism; D014700:Verapamil / Q000031:analogs & derivatives* / Q000494:pharmacology*
D005711:Gallopamil; D014700:Verapamil; D002118:Calcium