College of International Management, Ritsumeikan Asia Pacific University, Beppu 874-8577, Japan.
Int J Mol Sci. 2023 Jul 1;24(13):11000. doi: 10.3390/ijms241311000.
Because there are a limited number of animal models for psychiatric diseases that can be extrapolated to humans, drug repurposing has been actively pursued. This study was aimed at uncovering recent trends in drug repurposing approaches and new technologies that can predict efficacy on humans based on animal models used in psychiatric drug development. Psychiatric drugs that were approved by the FDA between 2002 and 2022 were listed, and the method of how the drug repurposing has been applied was analyzed. Drug repurposing has been increasingly applied to recently approved psychiatric drugs. The development concepts of psychiatric drugs that have been developed through drug repurposing over the past 20 years were found to be divided into six categories: new application exploration, reduction of side effects, improvement of symptom control, improvement of medication compliance, enhancement of drug efficacy, and reduction of drug-drug interactions. All repurposed drugs approved before 2016 used either prodrugs or active metabolites, while all drugs approved in 2021 and beyond used fixed-dose combinations with sophisticated ideas. SmartCube, which uses artificial intelligence to predict human drug efficacy from animal phenotypes, was developed and produced novel drugs that show clinical efficacy. Well-designed drug repurposing approaches and new technologies for predicting human drug efficacy based off of animal models would contribute to novel psychiatric drug development.
由于可外推至人类的精神疾病动物模型数量有限,因此积极寻求药物再利用。本研究旨在揭示基于精神药物开发中使用的动物模型来预测人类疗效的药物再利用方法和新技术的最新趋势。列出了 2002 年至 2022 年期间被 FDA 批准的精神药物,并分析了药物再利用的应用方法。药物再利用越来越多地应用于最近批准的精神药物。发现过去 20 年通过药物再利用开发的精神药物的开发概念分为六类:新应用探索、减少副作用、改善症状控制、提高用药依从性、增强药物疗效和减少药物相互作用。所有在 2016 年之前批准的重新定位药物都使用前药或活性代谢物,而 2021 年及以后批准的所有药物都使用具有复杂理念的固定剂量组合。使用人工智能从动物表型预测人类药物疗效的 SmartCube 已被开发并生产出具有临床疗效的新型药物。基于动物模型预测人类药物疗效的精心设计的药物再利用方法和新技术将有助于新型精神药物的开发。