DPI 201-106, a novel cardioactive agent. Combination of cAMP-independent positive inotropic, negative chronotropic, action potential prolonging and coronary dilatory properties

  • G. Scholtysik
  • R. Salzmann
  • R. Berthold
  • J. W. Herzig
  • U. Quast
  • R. Markstein


The in vitro cardiac effects of DPI 201-106, a novel piperazinyl-indole, were investigated.

DPI 201-106 produced concentration-dependent positive inotropic effects in guinea-pig and rat left atria, kitten, rabbit and guinea-pig papillary muscles and Langendorff perfused hearts of rabbits between 10−7 and 3×10−6 mol/l. During isometric twitches, contraction and relaxation phases were prolonged in guinea-pig left atria and right ventricular papillary muscles from kitten and guinea-pigs. Spontaneous sinus rate was decreased in right atria of guinea-pigs and rats. Coronary flow increased in rabbit isolated hearts. Functional refractory period was increased in left atria from guinea-pigs and rats with EC50 values of 1.7 and 0.24 μmol/l respectively.

In electrophysiological measurements, DPI 201-106 prolonged the action potential duration (APD70) in guinea-pig papillary muscles up to 70% and in rabbit atria up to 120% at 3 μmol/l. Other action potential characteristics were not changed in guinea-pig papillary muscles but Vmax was decreased in rabbit left atria. The electrophysiological as well as the positive inotropic effects were stereoselective with the activity residing in the S-enantiomer.

DPI 201-106 increased the Ca2+-sensitivity of skinned fibres from porcine trabecular septomarginalis with an EC50 of 0.2 nmol/l. DPI 201-106 did not change cAMP levels in guinea-pig atria and rabbit papillary muscles. Slow action potentials were not induced by DPI 201-106 in partially depolarized guinea-pig papillary muscles. Phosphodiesterase activity of rat hearts was not inhibited by DPI 201-106 at pharmacologically relevant concentrations. The presence of propranolol did not influence the inotropic potency of DPI 201-106 in guinea-pig atria.

In conclusion, DPI 201-106 represents a novel type of positive inotropic agents with a synergistic sarcolemmal and intracellular mechanism of action.

Key words

DPI 201-106 Positive inotropic effect Cardiac electrophysiology Stereoselectivity Ca2+-sensitization 


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Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • G. Scholtysik
    • 1
  • R. Salzmann
    • 1
  • R. Berthold
    • 1
  • J. W. Herzig
    • 1
  • U. Quast
    • 1
  • R. Markstein
    • 1
  1. 1.Preclinical ResearchSandoz Ltd.BaselSwitzerland

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