Ca-Agonists: a new class of inotropic drugs

  • M. Bechem
  • R. Gross
  • S. Hebisch
  • M. Schramm
Conference paper


The basic pharmacology of dihydropyridine Ca-agonists published so far (BAY k8644, CGP 28–392, H 160/51, YC 170, and 202–791) is described. The importance of the potency of the enantiomeres for the effect of a racemic compound is underlined.

The Ca agonist prototype BAY k8644 leads to an increase of the maximal rate of rise of left ventricular pressure (LV(dP/dt)) and an increase of left ventricular stroke work in conscious dogs. When the vascular effects of BAY k8644 are counterbalanced by intravenous injection of sodiumnitroprusside, the left ventricular functions curves show markedly increased stroke work against the same mean arterial blood pressure at the same filling pressure.

BAY k8644 stimulates the heart economically: the net efficiency in isolated working guinea-pig hearts is about 20%, identical to a stimulation by calcium or ouabain. Cardiotonic drugs acting via cAMP-dependent mechanisms like isoprenaline, amrinone, or pimobendane however, stimulate the heart about 1/3 less economically.

The mechanism of action of Ca-agonists is explained from electrophysiological findings: Ca-agonistic dihydropyridines increase the open probability of the Ca-channels by a shift of the open-probability curve to more negative membrane potentials. As a consequence, the steady-state inactivation curve of the Ca-channel is also shifted in the same direction. While the effect on open-probability is the underlying mechanism for Ca-agonism, the latter effect results in Ca-antagonism. Therefore, depending on drug concentration and on membrane resting potential, a single chemical compound can act either as a Ca-agonist or a Ca-antagonist. A kinetic model of dihydropyridine action on the Ca-channel is described.


Left Ventricular Pressure Positive Inotropic Effect Coronary Perfusion Pressure Racemic Compound Negative Membrane Potential 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • M. Bechem
    • 1
  • R. Gross
    • 2
  • S. Hebisch
    • 1
  • M. Schramm
    • 1
  1. 1.Institut für PharmakologieBayer AGWuppertalGermany
  2. 2.Institut für PharmakologieBayer AGWuppertal 1Germany

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