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Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

Potassium channel x Sodium channels

Mechanism

Potassium channel blockers, Sodium channels stimulants

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Cardiovascular Diseases

Inactive Indication

Heart Failure

Originator Organization

Johnson & Johnson

Active Organization

R.W. Johnson Pharmaceutical Research Institute

Inactive Organization

Johnson & Johnson

Drug Highest PhaseDiscovery

First Approval Date-

Regulation-

Structure

Molecular FormulaC25H26F2N6OS

InChIKeyJOMBZLFCXNSKEQ-UHFFFAOYSA-N

CAS Registry125363-87-3

We examined the effects of the cardiotonic agent RWJ 24517 (Carsatrin, racemate) and its (S)- and (R)-enantiomers on action potential duration, Na(+) current (I(Na)), and delayed rectifier K(+) current (I(K)) of guinea pig ventricular myocytes. RWJ 24517 (0. 1 and 1 microM) prolongation of action potential duration could not be accounted for by suppression of either the rapid (I(Kr)) or slow (I(Ks),) component of I(K), although RWJ 24517 did reduce I(Kr) at concentrations of 1 microM. A more dramatic effect of RWJ 24517 (0.1-1 microM) and the (S)-enantiomer of RWJ 24517 (0.1-3 microM) was an increase in peak I(Na) and slowing of the rate of I(Na) decay, eliciting a large steady-state current. Neither RWJ 24517 nor the (S)-enantiomer affected the fast time constant for I(Na) decay, but both significantly increased the slow time constant, in addition to increasing the proportion of I(Na) decaying at the slow rate. Both agents elicited a use-dependent decrease of peak I(Na) (3-10 microM), which probably resulted from a slowing of both fast and slow rates of recovery from inactivation. In contrast, the (R)-enantiomer of RWJ 24517 did not induce a steady-state component I(Na) or increase peak I(Na) up to 10 microM, but it decreased peak I(Na) at 30 microM. The (R)-enantiomer displayed little use-dependent reduction of I(Na) during trains of repetitive pulses and had no effect on rates of inactivation or recovery from inactivation. These actions of the racemate and the (S)-stereoisomer to slow inactivation and to prolong both Na(+) influx and action potential duration may contribute to the positive inotropic actions of these agents because the resulting accumulation of intracellular Na(+) would increase intracellular Ca(2+) via Na(+)/Ca(2+) exchange.

100 Deals associated with Carsatrin

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