Stereoselectivity of drug action

Chirality is a fundamental property of biological systems and reflects the underlying asymmetry of matter. Drug-receptor interactions have long been known to be stereoselective, and it is increasingly recognized that both pharmacodynamic and pharmacokinetic events contribute to the overall clinically observed stereoselectivity. The importance of this phenomenon has now been explicitly recognized by drug regulatory agencies who are issuing guidelines for drug development. This review outlines some of the scientific issues surrounding drug stereoselectivity, with particular emphasis being paid to drug interactions at ion channels where, because of state-dependent interactions, stereoselectivity is a moving target.