Romach M K, Glue P, Kampman K, Kaplan H L, Somer G R, Poole S, Clarke L, Coffin V, Cornish J, O'Brien C P, Sellers E M
Psychopharmacology and Dependence Research Unit, Centre for Research in Women's Health, Sunnybrook and Women's College Health Sciences Centre, Women's College Campus, Toronto, Ontario, Canada.
Arch Gen Psychiatry. 1999 Dec;56(12):1101-6. doi: 10.1001/archpsyc.56.12.1101.
The subjective and reinforcing effects of cocaine in humans are associated with the enhancement of endogenous dopamine function in the mesolimbic system. This study examined the role of dopamine D1-like receptors in the behavioral and mood effects of cocaine by evaluating the effects of the selective D1/D5 antagonist ecopipam (SCH 39166) on subjective responses to intravenous cocaine in 11 subjects with cocaine dependence as defined by DSM-IV.
Subjects were pretreated in a randomized double-blind fashion with either placebo or 10 mg, 25 mg, or 100 mg of ecopipam orally on 4 separate occasions. Two hours later a single intravenous injection of 30 mg of cocaine was administered. Subjective and cardiovascular responses were measured and blood samples for pharmacokinetic evaluation were obtained prior to cocaine dosing and at various times after dosing.
The euphoric (P = .004) and stimulating (P = .03) effects of cocaine were attenuated in a dose-dependent manner by ecopipam, while ratings of desire to take cocaine were diminished (P = .02). Ecopipam in combination with cocaine was safe and well tolerated.
These data indicate a potentially important role for D1-like receptors in the acute mood-altering and rewarding effects of cocaine in humans.
可卡因对人类的主观及强化作用与中脑边缘系统内源性多巴胺功能的增强有关。本研究通过评估选择性D1/D5拮抗剂依考哌唑（SCH 39166）对11名符合《精神疾病诊断与统计手册》第四版（DSM-IV）定义的可卡因依赖受试者静脉注射可卡因后主观反应的影响，来研究多巴胺D1样受体在可卡因行为和情绪效应中的作用。
受试者在4个不同场合以随机双盲方式分别接受安慰剂或10毫克、25毫克或100毫克依考哌唑口服预处理。两小时后静脉注射单次剂量30毫克可卡因。在给予可卡因之前及给药后的不同时间测量主观和心血管反应，并采集血样进行药代动力学评估。
依考哌唑以剂量依赖方式减弱了可卡因的欣快感（P = .004）和兴奋作用（P = .03），同时服用可卡因的欲望评分降低（P = .02）。依考哌唑与可卡因联用安全且耐受性良好。
这些数据表明D1样受体在可卡因对人类的急性情绪改变和奖赏效应中可能起重要作用。
Zotero 插件