Inhibition of the myocardial Ca(2+)-current (ICa) by the enantiomers of DPI 201-106 and BDF 8784.

Abstract:

: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 (ICa) 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 ICa in a concentration-dependent manner, the IC50 values were 1.1 mumol l-1 for racemic and S-DPI, and 1.2 mumol l-1 for R-DPI, respectively. Racemic, S- and R-BDF 8784 also reduced ICa, the respective IC50 values were 3.6 mumol l-1 for racemic BDF 8784, 1.3 mumol l-1 for S-BDF 8784 and 1.1 mumol l-1 for R-BDF 8784. 3. Neither the DPI nor the BDF 8784 enantiomers alter the time course of inactivation of ICa. The steady-state inactivation curve for ICa was shifted along the voltage axis to negative membrane potentials. The block of ICa was dependent on the membrane potential and increased with membrane depolarization. 4. Our findings indicate that DPI and BDF 8784 inhibit ICa in a non-stereoselective manner, which contrasts the opposite effects of the DPI enantiomers on Na+ channels.

journal_name

Br J Pharmacol

authors

Ravens U,Pfeifer T,Wettwer E,Grundke M

doi

10.1111/j.1476-5381.1991.tb12456.x

subject

Has Abstract

pub_date

1991-10-01 00:00:00

pages

490-4

issue

2

eissn

0007-1188

issn

1476-5381

journal_volume

104

pub_type

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