Vashistha Vinod Kumar, Sethi Sonika, Tyagi Inderjeet, Das Dipak Kumar
Department of Chemistry, GLA University, Mathura, Uttar Pradesh 281406, India.
Department of Chemistry, GD Goenka University, Gurgaon, Haryana 122103, India.
Asian Biomed (Res Rev News). 2022 Apr 29;16(2):55-69. doi: 10.2478/abm-2022-0008. eCollection 2022 Apr.
Stereochemistry plays an important role in drug design because the enantiomers of a drug frequently vary in their biological action and pharmacokinetic profiles. Racemates of a drug with either an inactive or an unsafe enantiomer can lead to detrimental effects. The manufacturing industry may still produce racemates, but such decisions must pass through rigorous analyses of the pharmacological and pharmacokinetic characteristics of the particular enantiomer related to the racemates. The pharmacokinetics of antidepressants or antidepressive agents is stereoselective and predominantly favors one enantiomer. The use of pure enantiomers offers (i) better specificity than the racemates in terms of certain pharmacological actions, (ii) enhanced clinical indications, and (iii) optimized pharmacokinetics. Therefore, controlling the stereoselectivity in the pharmacokinetics of antidepressive drugs is of critical importance in dealing with depression and psychiatric conditions. The objective of this review is to highlight the importance of the stereochemistry of antidepressants in the context of the design and development of new chirally pure pharmaceuticals, the potential complications caused by using racemates, and the benefits of using pure enantiomers.
立体化学在药物设计中起着重要作用，因为药物的对映体在其生物活性和药代动力学特征方面常常有所不同。含有无活性或不安全对映体的药物外消旋体可能会导致有害影响。制药行业可能仍会生产外消旋体，但此类决策必须经过对与该外消旋体相关的特定对映体的药理和药代动力学特性的严格分析。抗抑郁药或抗抑郁剂的药代动力学具有立体选择性，且主要有利于一种对映体。使用纯对映体在某些药理作用方面比外消旋体具有（i）更好的特异性，（ii）增强的临床适应症，以及（iii）优化的药代动力学。因此，控制抗抑郁药物药代动力学中的立体选择性对于治疗抑郁症和精神疾病至关重要。本综述的目的是强调抗抑郁药的立体化学在新型手性纯药物的设计和开发背景下的重要性、使用外消旋体可能引起的并发症以及使用纯对映体的益处。
