Wainer I W
Department of Oncology, McGill University, Montreal, Quebec, Canada.
Am J Hosp Pharm. 1992 Sep;49(9 Suppl 1):S4-8.
The relationship between the stereochemistry of drugs and their therapeutic and toxic effects is discussed. Molecular structures that have the same chemical constituents and are related to each other as an object and its nonsuperimposable mirror image are enantiomers. A molecule that has at least one pair of enantiomers is a chiral compound, and a 50:50 mixture of enantiomers is a racemic mixture. The enantiomers of a chiral drug may vary in their interactions with chiral or asymmetric environments such as enzymes and receptors. These variations may lead to differences in pharmacology, pharmacokinetics, therapeutic effect, efficacy, and toxicity. For example, dextropropoxyphene is an analgesic, whereas its mirror image, levopropoxyphene, is an antitussive agent. Enantiomers may have identical efficacy and toxicity. They may have the same therapeutic and toxic effects but differ in the magnitude of these effects; one may possess all the pharmacologic activity and the other may be biologically inactive, or both may be pharmacologically active but have qualitatively different therapeutic and toxic effects. Continued research into the stereochemistry of drugs may lead to the development of newer, safer, and more efficacious drugs and other chemical compounds.
本文讨论了药物的立体化学与其治疗作用和毒性作用之间的关系。具有相同化学成分且彼此相关，如同物体与其不可重叠的镜像的分子结构称为对映体。具有至少一对对映体组合的分子是手性化合物，对映体的 50:50 混合物是外消旋混合物。手性药物的对映体与手性或不对称环境（如酶和受体）相互作用时可能存在差异。这些差异可能导致药理学、药代动力学、治疗效果、疗效和毒性方面的不同。例如，右丙氧芬是一种镇痛药，而其镜像左丙氧芬是一种镇咳药。对映体可能具有相同的疗效和毒性。它们可能具有相同的治疗和毒性作用，但这些作用的程度不同；一个可能具有所有药理活性，另一个可能无生物活性，或者两者都可能具有药理活性，但在治疗和毒性作用上具有质的差异。对药物立体化学的持续研究可能会带来更新、更安全和更有效的药物及其他化合物的开发。
