Stereoisomers and Drug Toxicity

Abstract

All drugs produce adverse effects, though the risk varies widely between different compounds. Many toxic reactions are an extension of the mechanism responsible for the therapeutic effect and can be avoided by careful dose adjustment. Other adverse events are not related to the beneficial action of the drug. Recent interest has focused on the role of the different properties of individual drug enantiomers in causing drug toxicity. For drugs with a single chiral centre, both enantiomers may be therapeutically active. However, if the main therapeutic benefit is in only 1 enantiomer, several possibilities exist for the other enantiomer--inactive, a qualitatively different effect, an antagonistic effect or greater toxicity.

Recent applications of stereoselective chromatography

“…As a result of such chiral recognition, drug enantiomers may differ in their pharmacokinetic handling and their pharmacological and/or toxicological profiles. 3,4 For drugs with a single stereogenic center, both enantiomers may be pharmacologically active. However, if the main pharmacological effect is in only one enantiomer, several possibilities exist for the other enantiomer: inactivity, a qualitatively different effect, an antagonistic effect, or severe toxicity.…”

Microreaction and membrane technologies for continuous single-enantiomer production: A review

“…[7] Other examples of differences between enantiomers are also mirrored by pharmaceutical drugs and their therapeutic effects. [8,9] The administration of enantiomerically impure drugs, in particular, may have fatal consequences, such as the tragedy caused by thalidomide. [10] Unlike (S)thalidomide, which acts as a sedative, its R stereoisomer disrupts fetal development.…”

Enantioselective molecular sensing of aromatic amines using tetra-(S)-di-2-naphthylprolinol calix[4]arene

“…Since most drug effects are due to interactions with chiral biological materials, each enantiomer may have different pharmacological properties in terms of activity, potency, toxicity, transport mechanism and metabolic route. 2 Methods employed in the pharmaceutical industry for the determination of enantiomeric composition include liquid 3 and gas chromatography 4 and capillary electrophoresis. 5 Other techniques such as polarimetry, circular dichroism, 6 absorbance spectrometry, 7 infrared transmission spectrometry, 8 X-ray anomalous scattering, 9 and NMR spectroscopy 10 have also been used.…”