Pharmacotherapeutics for treatment of psychostimulant use disorder are still an unmet medical goal. Recently, off label use of modafinil (MOD), an approved medication for treatment of sleep disturbances, has been tested as a therapeutic for cocaine and methamphetamine use disorder. Positive results have been found in subjects dependent on psychostimulants without concurrent abuse of other substances. Novel structural analogs of MOD have been synthesized in the search for compounds with potentially broader therapeutic efficacy than the parent drug. In the present report we review their potential efficacy as treatments for psychostimulant abuse and dependence assessed in preclinical tests. Results from these preclinical proof of concept studies reveal that some modafinil analogs do not possess typical cocaine-like neurochemical and behavioral effects. Further, they might blunt the reinforcing effects of psychostimulants in animal models, suggesting their potential efficacy as pharmacotherapeutics for treatment of psychostimulant use disorders.

治疗精神兴奋剂使用障碍的药物治疗仍然是一个未实现的医学目标。最近，莫达非尼 (MOD) 的标签外使用已被测试为可卡因和甲基苯丙胺使用障碍的治疗药物，这是一种获准用于治疗睡眠障碍的药物。在依赖精神兴奋剂而没有同时滥用其他物质的受试者中发现了积极的结果。MOD 的新型结构类似物已被合成以寻找比母体药物具有潜在更广泛治疗功效的化合物。在本报告中，我们回顾了它们作为临床前测试评估的精神兴奋剂滥用和依赖治疗的潜在疗效。这些临床前概念验证研究的结果表明，一些莫达非尼类似物不具有典型的可卡因样神经化学和行为效应。此外，它们可能会削弱动物模型中精神兴奋剂的增强作用，表明它们作为治疗精神兴奋剂使用障碍的药物治疗的潜在功效。