多巴胺 D1 和 D3 受体的多药理学作为物质使用障碍的一种潜在治疗方法。
Dopamine D1 and D3 receptor polypharmacology as a potential treatment approach for substance use disorder.
机构信息
The Graduate Center of the City University of New York, 365 Fifth Avenue, New York, NY 10016, USA.
The Graduate Center of the City University of New York, 365 Fifth Avenue, New York, NY 10016, USA; Department of Psychology, Queens College, City University of New York, 65-30 Kissena Blvd, Flushing NY 11367, USA.
出版信息
Neurosci Biobehav Rev. 2018 Jun;89:13-28. doi: 10.1016/j.neubiorev.2018.03.020. Epub 2018 Mar 22.
In the search for efficacious pharmacotherapies to treat cocaine addiction much attention has been given to agents targeting dopamine D1 or D3 receptors because of the involvement of these receptors in drug-related behaviors. D1-like and D3 receptor partial agonists and antagonists have been shown to reduce drug reward, reinstatement of drug seeking and conditioned place preference in rodents and non-human primates. However, translation of these encouraging results to clinical settings has been limited due to a number of factors including toxicity, poor pharmacokinetic properties and extrapyramidal and sedative side effects. This review highlights the role of D1 and D3 receptors in drug reward and seeking, the discovery of D1-D3 heteromers and their potential as targets in the treatment of addiction.
在寻找有效的药物治疗可卡因成瘾的过程中，由于这些受体参与了与药物相关的行为，因此人们非常关注靶向多巴胺 D1 或 D3 受体的药物。D1 样和 D3 受体部分激动剂和拮抗剂已被证明可减少啮齿动物和非人类灵长类动物的药物奖励、药物寻求的恢复和条件性位置偏好。然而，由于包括毒性、较差的药代动力学特性以及锥体外系和镇静副作用在内的多种因素，这些令人鼓舞的结果在临床环境中的转化受到限制。本综述强调了 D1 和 D3 受体在药物奖励和寻求中的作用，以及 D1-D3 异源二聚体的发现及其作为治疗成瘾的靶点的潜力。
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