Platt Donna M, Rowlett James K, Spealman Roger D
Harvard Medical School, New England Regional Primate Research Center, One Pine Hill Drive, PO Box 9102, Southborough, MA 01772-9102, USA.
Psychopharmacology (Berl). 2002 Oct;163(3-4):265-82. doi: 10.1007/s00213-002-1137-8. Epub 2002 Jul 17.
The illicit use of cocaine is a persistent health problem worldwide. Currently, there are no broadly effective pharmacotherapies to treat cocaine addiction. A prerequisite for development of useful anti-cocaine medications is an understanding of the pharmacological basis of cocaine's effects. The functional analysis of behavior in laboratory animals has allowed for the development of strategies identifying candidate medications to treat cocaine addiction.
This review summarizes the current status of dopaminergic compounds as cocaine pharmacotherapies in animal models of cocaine addiction.
Maintenance medications should share key subjective effects with cocaine, yet have limited abuse liability and side effects. However, maintenance medications often have reinforcing effects that could contribute to abuse potential and side effects that could deter patient compliance. Combined with cocaine, these drugs enhance cocaine's effects. Cocaine antagonists should block the effects of cocaine and have no cocaine-like effects or side effects on their own. However, the cocaine-modulating effects of candidate cocaine antagonists are often surmountable, and, on their own, these drugs produce severe motoric side effects. In contrast, dopamine (DA) partial agonists should exhibit reduced abuse potential relative to agonists, as well as less severe motoric effects relative to antagonists. Combined with cocaine, these drugs should antagonize cocaine's effects.
DA partial agonists, in particular the D(3)-selective and the D1-like partial agonists, offer a more encouraging profile for novel anti-cocaine medications. Neither class of drug is self-administered, and side effects are often less severe and only observed at doses above those that antagonize the effects of cocaine.
可卡因的非法使用是全球持续存在的健康问题。目前，尚无广泛有效的药物疗法来治疗可卡因成瘾。开发有效的抗可卡因药物的一个先决条件是了解可卡因作用的药理学基础。对实验动物行为的功能分析有助于制定策略，以识别治疗可卡因成瘾的候选药物。
本综述总结了多巴胺能化合物作为可卡因成瘾动物模型中可卡因药物疗法的现状。
维持药物应与可卡因具有相同的关键主观效应，但滥用可能性和副作用有限。然而，维持药物往往具有强化作用，可能导致滥用潜力，其副作用可能会妨碍患者的依从性。与可卡因联合使用时，这些药物会增强可卡因的作用。可卡因拮抗剂应能阻断可卡因的作用，且自身无类似可卡因的作用或副作用。然而，候选可卡因拮抗剂对可卡因的调节作用往往是可克服的，而且这些药物本身会产生严重的运动副作用。相比之下，多巴胺（DA）部分激动剂相对于激动剂应具有较低的滥用潜力，相对于拮抗剂应具有较轻的运动效应。与可卡因联合使用时，这些药物应能拮抗可卡因的作用。
DA部分激动剂，特别是D(3)选择性和D1样部分激动剂，为新型抗可卡因药物提供了更令人鼓舞的前景。这两类药物都不会被自我给药，副作用通常较轻，且只有在高于拮抗可卡因作用的剂量时才会出现。
