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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Strategy for a Genetic Assessment of Antipsychotic and Antidepressant- Related Proarrhythmia

Author(s): Antonio Drago, Fabrizio De Ponti, Giuseppe Boriani, Diana De Ronchi and Alessandro Serretti

Volume 15 , Issue 24 , 2008

Page: [2472 - 2517] Pages: 46

DOI: 10.2174/092986708785909058

Price: $65

Abstract

Antidepressants and antipsychotics may affect several ion channels involved in the control of cardiac action potential and be proarrhythmic. In this field, accurate understanding of genetics, which per se is a non-controllable risk factor, may help clinicians to prevent life-threatening side effects. So far, a number of genes have been associated with arrhythmia: SCN5A, SCN4B, CACNL1AC, KCNH2, KCNQ1, KCNE1, ANK2, ALG10, KCNJ2, KCNE2, RYR2, KCND3, KCND2, ACE, NOS1AP, CASQ2 and Rad. These genes represent good candidates for the definition of a genetic pro-arrhythmic profile. A genetic analysis of these targets is provided and their possible pathophysiological role in arrhythmias is discussed. Special attention is devoted to the interactions between these genes and new generation antidepressants and antipsychotics. A list of relevant rare mutations within the selected genes is presented, together with a complete list of Tag SNPs covering the whole genetic sequence. The aim of this paper is to define a part of the genetic framework responsible for the proarrhythmic effects of antidepressants and antipsychotics. The selected variants, both mutations and polymorphisms, may help in defining a next-to-come genetic assessment to be performed before drug prescription in order to improve drug safety.

Keywords: Pharmacogenetics, arrhythmia, cardiotoxicity, adverse events, antipsychotics, antidepressants, long QT


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