Cardiac Na+ channel activation as a positive inotropic principle.

Abstract:

:This article reviews the relation of cardiac cellular Na+ load and increased force of contraction. Digitalis glycosides and naturally occurring Na+ channel activators are considered. DPI201-106 was described as the first synthetic organic molecule with cardioselective Na+ channel-activating properties and investigated in clinical studies. Its pharmacology is reviewed. DPI 201-106 prolongs the open state of cardiac Na+ channels. This effect represents the primary mechanism of its positive inotropic effect. The involvement of cAMP is excluded. Ca2+ antagonistic and local anaesthetic effects are assumed to contribute advantageously to the pharmacodynamic profile of DPI 201-106. Chemically and pharmacologically related to DPI 201-106 is the new compound SDZ 210-921 for which original results are presented. It is concluded that DPI 201-106 represents the lead structure of a new class of cardiotonics with selective cardiac Na+ channel activation. DPI 201-106 and related compounds may serve as promising tools in the investigation of cardiac Na+ channel-gating dynamics, in addition to their therapeutic potential.

journal_name

J Cardiovasc Pharmacol

authors

Scholtysik G

doi

10.1097/00005344-198914003-00006

subject

Has Abstract

pub_date

1989-01-01 00:00:00

pages

S24-9

eissn

0160-2446

issn

1533-4023

journal_volume

14 Suppl 3

pub_type

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