Dwoskin Linda P, Rauhut Anthony S, King-Pospisil Kelley A, Bardo Michael T
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
CNS Drug Rev. 2006 Fall-Winter;12(3-4):178-207. doi: 10.1111/j.1527-3458.2006.00178.x.
Bupropion hydrochloride ((+/-)-2-tert-butylamino)-3'-chloropropiophenone x HCl) is a nonselective inhibitor of the dopamine transporter (DAT) and the norepinephrine transporter (NET) and is also an antagonist at neuronal nicotinic acetylcholine receptors (nAChRs). In animal models used commonly to screen for antidepressant activity, bupropion shows a positive response. Also using animal models, bupropion has been shown to attenuate nicotine-induced unconditioned behaviors, to share or enhance discriminative stimulus properties of nicotine and to have a complex effect on nicotine self-administration, i.e., low doses augmenting nicotine self-administration and high doses attenuating self-administration. Current studies show that bupropion facilitates the acquisition of nicotine conditioned place preference in rats, further suggesting that bupropion enhances the rewarding properties of nicotine. Bupropion has been shown to attenuate the expression of nicotine withdrawal symptoms in both animal models and human subjects. With respect to relapse, current studies show that bupropion attenuates nicotine-induced reinstatement in rats, but large individual differences are apparent. Clinically, bupropion is used as a treatment for two indications, as an antidepressant, the indication for which it was developed, and as a tobacco use cessation agent. In clinical trials, bupropion is being tested as a candidate treatment for psychostimulant drug abuse, attention-deficit hyperactivity disorder (ADHD) and obesity. Bupropion is available in three bioequivalent oral formulations, immediate release (IR), sustained release (SR), and extended release (XL). Extensive hepatic metabolism of bupropion produces three pharmacologically active metabolites, which may contribute to its clinical profile.
盐酸安非他酮（(+/-)-2-叔丁氨基）-3'-氯苯丙酮·xHCl）是多巴胺转运体（DAT）和去甲肾上腺素转运体（NET）的非选择性抑制剂，也是神经元烟碱型乙酰胆碱受体（nAChRs）的拮抗剂。在常用于筛选抗抑郁活性的动物模型中，安非他酮呈现阳性反应。同样利用动物模型，已表明安非他酮可减弱尼古丁诱导的非条件性行为，具有或增强尼古丁的辨别性刺激特性，并对尼古丁自我给药有复杂影响，即低剂量增强尼古丁自我给药，高剂量减弱自我给药。当前研究表明，安非他酮促进大鼠尼古丁条件性位置偏爱形成，进一步提示安非他酮增强尼古丁的奖赏特性。在动物模型和人类受试者中，均已表明安非他酮可减轻尼古丁戒断症状的表达。关于复吸，当前研究表明，安非他酮可减弱大鼠尼古丁诱导的复吸，但个体差异明显。临床上，安非他酮用于两种适应症的治疗，一是作为抗抑郁药，即其研发的适应症，二是作为戒烟药。在临床试验中，安非他酮正作为精神兴奋药滥用、注意力缺陷多动障碍（ADHD）和肥胖症的候选治疗药物进行测试。安非他酮有三种生物等效的口服制剂，即速释（IR）、缓释（SR）和长效释放（XL）。安非他酮广泛的肝脏代谢产生三种具有药理活性的代谢产物，这可能有助于其临床特征表现。
