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Inhibition of the myocardial Ca 2+ ‐current ( I Ca ) by the enantiomers of DPI 201–106 and BDF 8784
Author(s) -
Ravens Ursula,
Pfeifer Thomas,
Wettwer Erich,
Grundke Martin
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12456.x
Subject(s) - enantiomer , stereoselectivity , chemistry , depolarization , racemic mixture , membrane potential , membrane , stereochemistry , biophysics , biochemistry , biology , catalysis
1 We studied the stereoselectivity of the effects of the enantiomers of the cardiotonic agent DPI 201–106 (4‐[3′‐(4″‐benzhydryl‐1″‐piperazinyl)‐2′‐hydroxypropoxy]‐1H‐indole‐2‐carbonitrile, DPI) and its methyl‐for‐carbonitrile analogue BDF 8784 on cardiac calcium currents ( I Ca ) of guinea‐pig ventricular myocytes. The actions of the S‐ and R ‐enantiomers were compared with those of the racemate. 2 Racemic, S‐ and R ‐DPI depressed I Ca in a concentration‐dependent manner, the IC 50 values were 1.1 μmol 1 −1 for racemic and S‐DPI, and 1.2 μmol 1 −1 for R ‐DPI, respectively. Racemic, S‐ and R ‐BDF 8784 also reduced I Ca , the respective IC 50 values were 3.6 μmol 1 −1 for racemic BDF 8784, 1.3 μmol 1 −1 for S‐BDF 8784 and 1.1 μmol 1 −1 for R ‐BDF 8784. 3 Neither the DPI nor the BDF 8784 enantiomers alter the time course of inactivation of I Ca . The steady‐state inactivation curve for I Ca was shifted along the voltage axis to negative membrane potentials. The block of I Ca was dependent on the membrane potential and increased with membrane depolarization. 4 Our findings indicate that DPI and BDF 8784 inhibit I Ca in a non‐stereoselective manner, which contrasts the opposite effects of the DPI enantiomers on Na + channels.