Effects of ecopipam, a selective dopamine D1 antagonist, on smoked cocaine self-administration by humans.
BACKGROUND
Data obtained in laboratory animals and humans suggest that dopamine D1 receptor antagonists decrease cocaine self-administration and block cocaine's discriminative stimulus and subjective effects.


OBJECTIVE
This study investigates the effects of the selective dopamine D1 antagonist, ecopipam (SCH 39166), on the reinforcing, cardiovascular, and subjective effects of cocaine in humans.


METHODS
Ten non-treatment-seeking cocaine smokers (two females, eight males), residing on an inpatient research unit, were maintained on placebo and ecopipam (100 mg p.o.) in random order using a within-subjects, cross-over design. Cocaine self-administration (0, 12, 25, and 50 mg) was tested beginning on the 5th day of each 8-day maintenance condition. A six-trial choice procedure (cocaine vs $5 merchandise vouchers) was utilized, with sessions consisting of one sample trial, when participants smoked the cocaine dose available that day, and five choice trials, when participants chose between smoking the available cocaine dose or receiving one merchandise voucher.


RESULTS
In the presence of placebo cocaine, ecopipam significantly decreased cocaine craving while increasing alcohol and tobacco craving. In the presence of active cocaine, ecopipam increased cocaine self-administration (12 mg) and increased ratings of "good drug effect," "high," "stimulated," and dose quality (25 and 50 mg). Ecopipam produced small but significant increases in blood pressure, regardless of cocaine dose.


CONCLUSIONS
Maintenance on the long-acting dopamine D1 antagonist, ecopipam, enhanced both cocaine self-administration as well as its subjective effects compared to maintenance on placebo. These data suggest that chronic antagonism of the dopamine D1 receptor may not be a useful approach for the treatment of cocaine abuse.
Haney
M
M
Department of Psychiatry, College of Physicians and Surgeons of Columbia University and Division on Substance Abuse, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA. mh235@columbia.edu
Ward
A S
AS
Foltin
R W
RW
Fischman
M W
MW
D000280:Administration, Inhalation; D000328:Adult; D001552:Benzazepines / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003042:Cocaine / Q000097:blood; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000523:psychology; D018592:Cross-Over Studies; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018765:Dopamine Uptake Inhibitors / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012646:Self Administration
D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; C058081:ecopipam; D003042:Cocaine