Review of the genotoxic properties of chlorpromazine and related phenothiazines

Abstract

Chlorpromazine and related phenothiazine drugs have been used in human and veterinary medications for more than 40 years, predominantly as psychotropic agents. Genotoxicity reports are in many cases of relatively antiquated test design. Overall there appears to be no genotoxic activity associated with these drugs when tested under standard conditions. Limited evidence for the potential to form mutagenic nitrosation products and some indication for the ability to modulate the genotoxic action of various mutagens have been presented in the literature. UV irradiation of chlorpromazine and other chlorinated derivatives produces reactive free radicals which possess DNA damaging properties. Induction of gene mutation and chromosomal aberrations have been observed in appropriately designed photomutagenesis experiments. Enhancement but also reduction of UV induced skin tumour formation by chlorpromazine have been found. The decisive factor for the discrepant actions has not been recognized. It is clearly advisable to avoid extensive UV exposure during therapy with these drugs.