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Attenuation of the Euphoric Effects of Cocaine by the Dopamine D1/D5 Antagonist Ecopipam (SCH 39166)
Myroslava K. Romach, MSc, MD;
Paul Glue, MD, PhD;
Kyle Kampman, MD;
Howard L. Kaplan, PhD;
Gail R. Somer, MA;
Sabrina Poole;
Laura Clarke, RN;
Vicki Coffin, PhD;
James Cornish, MD;
Charles P. O'Brien, MD, PhD;
Edward M. Sellers, MD, PhD
Arch Gen Psychiatry. 1999;56:1101-1106.
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.
From the Psychopharmacology and Dependence Research Unit, Centre for Research in Women's Health, Sunnybrook and Women's College Health Sciences Centre, Women's College Campus (Drs Romach, Kaplan, and Sellers and Ms Somer), and the Departments of Pharmacology (Dr Sellers), Medicine (Dr Sellers), and Psychiatry (Drs Romach and Sellers), University of Toronto, Toronto, Ontario; Centre for Addiction and Mental Health, Toronto (Drs Kaplan and Sellers); University of Pennsylvania Treatment Research Center, Philadelphia (Drs Kampman, Cornish, and O'Brien and Ms Poole); and Schering Plough Research Institute, Kenilworth, NJ (Drs Glue and Coffin and Ms Clarke).
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