Insights into the effects of diclofenac and other non-steroidal anti-inflammatory agents on ion channels

Abstract

Diclofenac and other non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of inflammation and pain. Most effects of NSAIDs are attributed to the inhibition of cyclooxygenases (COX). However, many NSAIDs may have other effects not related to COX, including the modulation of various ion channels. The clinical implications of the effects on channels are not fully understood. This review outlines the effects of NSAIDs, with special attention to diclofenac, on ion channels and highlights the possible underlying mechanisms. NSAIDs have effects on channels such as inhibition, activation or changes in expression patterns. The channels affected include voltage-gated Na(+) , Ca(2+) , or K(+) channels, ligand-gated K(+) channels, transient receptor potential and other cation channels as well as chloride channels in several types of cells. The mechanisms of drug actions not related to COX inhibition may involve drug-channel interactions, interference with the generation of second messengers, changes in channel expression, or synergistic/antagonist interactions with other channel modulators. The effects on ion channels may account for novel therapeutic actions of NSAIDs or for adverse effects. Among the NSAIDs, diclofenac may serve as a template for developing new channel modulators and as a tool for investigating the actions of other drugs.