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PMID: 2991779 Published · ppublish English Journal Article

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

Naunyn-Schmiedeberg's archives of pharmacology ·Vol. 329 ·No. 3 ·1985-05-00 ·Pages 316-25

Scholtysik G, Salzmann R, Berthold R, Herzig JW, Quast U, Markstein R

Abstract

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 X 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 mumol/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 mumol/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 trabecula septomarginalis with an EC50 of 0.2 nmol/l. DPI 201-106 dit 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.

MeSH Terms
Action Potentials/drug effects Animals Cats Cyclic AMP/physiology Female Guinea Pigs Heart/drug effects Heart Rate/drug effects Male Myocardial Contraction/drug effects Phosphoric Diester Hydrolases/metabolism Piperazines/pharmacology Propranolol/pharmacology Protein Kinase Inhibitors Rabbits Sarcolemma/drug effects Stereoisomerism
Chemicals
Piperazines Protein Kinase Inhibitors DPI 201-106 Propranolol Cyclic AMP Phosphoric Diester Hydrolases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Scholtysik G
Salzmann R
Berthold R
Herzig J W
Quast U
Markstein R
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Article Info
Journal
Naunyn-Schmiedeberg's archives of pharmacology
Abbr.
Naunyn Schmiedebergs Arch Pharmacol
ISSN
0028-1298
DOI
10.1007/BF00501887
Published
1985-05-00
Pages
316-25
Language
English
Region
Germany
NLM ID
0326264
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00501887 View journal details
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