Attenuation of the euphoric effects of cocaine by the dopamine D1/D5 antagonist ecopipam (SCH 39166)

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

These data indicate a potentially important role for D1-like receptors in the acute mood-altering and rewarding effects of cocaine in humans.

• Authors: M K Romach, P Glue, K Kampman, H L Kaplan, G R Somer, S Poole, L Clarke, V Coffin, J Cornish, C P O'Brien, E M Sellers
• Journal: Archives of general psychiatry (Arch Gen Psychiatry) Vol. 56 Issue 12 Pg. 1101-6 (Dec 1999) ISSN: 0003-990X [Print] United States
• PMID: 10591286 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• Benzazepines
• Dopamine Antagonists
• Receptors, Dopamine
• ecopipam
• Cocaine

Topics

• Adult
• Behavior, Addictive (prevention & control, psychology)
• Benzazepines (pharmacology, therapeutic use)
• Cocaine (antagonists & inhibitors, pharmacology)
• Cocaine-Related Disorders (physiopathology, prevention & control, psychology)
• Dopamine Antagonists (pharmacology, therapeutic use)
• Euphoria (drug effects)
• Female
• Humans
• Male
• Receptors, Dopamine (drug effects, physiology)
• Reward