The potential of Na+/Ca2+ exchange blockers in the treatment of cardiac disease

Ion A. Hobai, Brian O'Rourke

Research output: Contribution to journalArticle

Abstract

The Na+/Ca2+ exchanger (NCX), a surface membrane antiporter, is the primary pathway for Ca2+ efflux from the cardiac cell and a determinant of both the electrical and contractile state of the heart. Enhanced expression of NCX has recently been recognised as one of the molecular mechanisms that contributes to reduced Ca2+ release, impaired contractility and an increased risk of arrhythmias during the development of cardiac hypertrophy and failure. The NCX has also been implicated in the mechanism of arrhythmias and cellular injury associated with ischaemia and reperfusion. Hence, NCX blockade represents a potential therapeutic strategy for treating cardiac disease, however, its reversibility and electrogenic properties must be taken into consideration when predicting the outcome. NCX inhibition has been demonstrated to be protective against ischaemic injury and to have a positive inotropic and antiarrhythmic effect in failing heart cells. However, progress has been impaired by the absence of clinically useful agents. Two drugs, KB-R7943 and SEA-0400, have been developed as NCX blockers but both lack specificity. Selective peptide inhibitors have been well characterised but are active only when delivered to the intracellular space. Gene therapy strategies may circumvent the latter problem in the future. This review discusses the effects of NCX blockade, supporting its potential as a new cardiovascular therapeutic strategy. 2004

Original languageEnglish (US)
Pages (from-to)653-664
Number of pages12
JournalExpert Opinion on Investigational Drugs
Volume13
Issue number6
DOIs
StatePublished - Jun 2004

Fingerprint

Cardiac Arrhythmias
Heart Diseases
Intracellular Space
Antiporters
Wounds and Injuries
Cardiomegaly
Genetic Therapy
Reperfusion
Ischemia
Heart Failure
Peptides
Membranes
Therapeutics
Pharmaceutical Preparations
SEA 0400
2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate

Keywords

  • Arrythmias
  • Heart failure
  • Ischaemia
  • Na/Ca exchanger
  • Positive inotropes

ASJC Scopus subject areas

  • Pharmacology

Cite this

The potential of Na+/Ca2+ exchange blockers in the treatment of cardiac disease. / Hobai, Ion A.; O'Rourke, Brian.

In: Expert Opinion on Investigational Drugs, Vol. 13, No. 6, 06.2004, p. 653-664.

Research output: Contribution to journalArticle

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