Medication Development Program, NIDA IRP, Baltimore, MD 21224, USA.
Molecules. 2023 Jul 7;28(13):5270. doi: 10.3390/molecules28135270.
Psychostimulant use disorders (PSUD) affect a growing number of men and women and exert sizable public health and economic burdens on our global society. Notably, there are some sex differences in the onset of dependence, relapse rates, and treatment success with PSUD observed in preclinical and clinical studies. The subtle sex differences observed in the behavioral aspects of PSUD may be associated with differences in the neurochemistry of the dopaminergic system between sexes. Preclinically, psychostimulants have been shown to increase synaptic dopamine (DA) levels and may downregulate the dopamine transporter (DAT). This effect is greatest in females during the high estradiol phase of the estrous cycle. Interestingly, women have been shown to be more likely to begin drug use at younger ages and report higher levels of desire to use cocaine than males. Even though there is currently no FDA-approved medication, modafinil, a DAT inhibitor approved for use in the treatment of narcolepsy and sleep disorders, has shown promise in the treatment of PSUD among specific populations of affected individuals. In this review, we highlight the therapeutic potential of modafinil and other atypical DAT inhibitors focusing on the lack of sex differences in the actions of these agents.
精神兴奋剂使用障碍（PSUD）影响着越来越多的男性和女性，给我们的全球社会带来了相当大的公共卫生和经济负担。值得注意的是，在临床前和临床研究中观察到，PSUD 的依赖发作、复发率和治疗成功率存在一些性别差异。在 PSUD 的行为方面观察到的细微性别差异可能与性别之间多巴胺能系统的神经化学差异有关。在临床前研究中，已经表明精神兴奋剂会增加突触多巴胺（DA）水平，并可能下调多巴胺转运蛋白（DAT）。在发情周期的高雌激素阶段，这种影响在女性中最为明显。有趣的是，与男性相比，女性更有可能在年轻时开始使用药物，并报告更高的可卡因使用欲望。尽管目前没有获得 FDA 批准的药物，但莫达非尼是一种 DAT 抑制剂，已被批准用于治疗嗜睡症和睡眠障碍，它在治疗特定人群的 PSUD 方面显示出了潜力。在这篇综述中，我们强调了莫达非尼和其他非典型 DAT 抑制剂的治疗潜力，重点关注这些药物在作用方面缺乏性别差异。
