Calcium Antagonistic Activity and Myocardial Ischemic Protection by Both Stereoisomers of Verapamil

  • M. Raschack
  • K. Engelmann


The effects of the optical isomers of verapamil were compared on intact and partially ischemic pig hearts as well as on vascular smooth muscle of rabbits and rats. In K+-depolarized strips of rabbit mesenteric artery, both isomers shifted calcium dose-response curves (tension development) in a qualitatively similar manner to the right, with threshold concentrations of 10–8 m (—)verapamil and 10–7 m (+)verapamil. In K+-depolarized rat aortic strips, the calcium antagonistic activity was quantified. (+)Verapamil was at least as potent as several other coronary drugs [(±)verapamil = 1]: perhexiline 0.02, prenylamine 0.05, fendiline 0.05, diltiazem 0.15, (±)verapamil 0.15, (-)verapamil 1.5. The optical isomers of D600 showed a considerably greater difference in calcium antagonistic potency (about a factor of 60) as compared to verapamil (factor of 10). In the pig heart, reversible and reproducible ischemia reactions were provoked by repeated occlusions (3 min) of a branch of the LAD followed by reperfusion for 15 min. In the tested range of 0.4–2.0 mg/kg i.V., (-I-)verapamil dose-dependently reduced ischemic ST elevations in four epicardial leads. At an intermediate dose of 1 mg/kg, (+Verapamil diminished ST-elevations by 32% (occlusion 11 min p.i.). Results not statistically different were obtained with 0.1 mg/kg (-)verapamil (28%) and 0.2 mg/kg (±)verapamil (40%). No qualitative differences between the isomers could be observed with regard to hemodynamic parameters with equieffective reduction of the ischemia reaction: slight decrease in heart rate; prolongation of PQ duration with only minimal and insignificant effect of (+)verapamil; decrease of systolic and diastolic blood pressure, left ventricular pressure, and LV dp/dt max . In contrast to optically active and racemic verapamil, nifedipine in a hypotensive dose (0.05 mg/kg i.v.) increased heart rate and diminished ischemic ST elevations only moderately (13%). The results obtained on vascular smooth muscle and ischemic pig heart clearly show that there are no remarkable qualitative differences between verapamil enantiomers. It can be concluded that (+)verapamil, by its calcium antagonistic properties, contributes to the therapeutic efficacy of the racemic drug.


Optical Isomer Epicardial Lead Racemic Drug Rabbit Mesenteric Artery Hypotensive Dose 
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Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • M. Raschack
    • 1
  • K. Engelmann
    • 1
  1. 1.Department of PharmacologyKnoll AGLudwigshafenFederal Republic of Germany

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