TY - JOUR
T1 - Repeated administration of the D1/5 antagonist ecopipam fails to attenuate the subjective effects of cocaine
AU - Nann-Vernotica, E.
AU - Donny, E. C.
AU - Bigelow, G. E.
AU - Walsh, S. L.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - Rationale: Dopaminergic compounds have been targeted as potential treatments for cocaine abuse because of the known role of dopamine systems in drug reinforcement. Recent preclinical and human data have focused on the D1/5 antagonist, SCH 39166 (ecopipam), as a potential therapeutic agent. Objectives: The objective of the present study was to determine whether treatment with chronic ecopipam can blunt or block the subjective effects of cocaine in the absence of significant behavioral impairment or toxic physiological effects. Methods: Four doses of ecopipam (0, 10, 25, and 100 mg p.o.) were administered daily for 1 week each in double-blind, random order to inpatient cocaine-dependent volunteers (n=10). Cocaine challenge doses (0, 25, and 50 mg/70 kg i.v.) were administered on the 7th day in ascending order, 1 h apart. Results: Ecopipam alone produced reliable dose-dependent deficits in performance on the digit symbol substitution task (DSST) and the circular lights task, but not a balance task. Impairment on the DSST waned with repeated dosing suggesting the development of tolerance. Ecopipam resulted in few direct subjective effects. Cocaine alone produced dose-dependent changes in prototypic subjective and physiological measures, however, ecopipam largely failed to alter either cocaine's direct effects or the desire for cocaine. Conclusions: Although the performance effects verify that these doses of ecopipam were behaviorally active, the absence of an attenuation of cocaine's effects or craving for cocaine in this chronic dosing paradigm suggests this compound is unlikely to be an effective pharmacotherapy for cocaine abuse.
AB - Rationale: Dopaminergic compounds have been targeted as potential treatments for cocaine abuse because of the known role of dopamine systems in drug reinforcement. Recent preclinical and human data have focused on the D1/5 antagonist, SCH 39166 (ecopipam), as a potential therapeutic agent. Objectives: The objective of the present study was to determine whether treatment with chronic ecopipam can blunt or block the subjective effects of cocaine in the absence of significant behavioral impairment or toxic physiological effects. Methods: Four doses of ecopipam (0, 10, 25, and 100 mg p.o.) were administered daily for 1 week each in double-blind, random order to inpatient cocaine-dependent volunteers (n=10). Cocaine challenge doses (0, 25, and 50 mg/70 kg i.v.) were administered on the 7th day in ascending order, 1 h apart. Results: Ecopipam alone produced reliable dose-dependent deficits in performance on the digit symbol substitution task (DSST) and the circular lights task, but not a balance task. Impairment on the DSST waned with repeated dosing suggesting the development of tolerance. Ecopipam resulted in few direct subjective effects. Cocaine alone produced dose-dependent changes in prototypic subjective and physiological measures, however, ecopipam largely failed to alter either cocaine's direct effects or the desire for cocaine. Conclusions: Although the performance effects verify that these doses of ecopipam were behaviorally active, the absence of an attenuation of cocaine's effects or craving for cocaine in this chronic dosing paradigm suggests this compound is unlikely to be an effective pharmacotherapy for cocaine abuse.
KW - Cardiovascular
KW - Cocaine
KW - Dopamine
KW - Nicotine
KW - Pharmacotherapy
KW - Smoking
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U2 - 10.1007/s002130100724
DO - 10.1007/s002130100724
M3 - Article
C2 - 11441423
AN - SCOPUS:0034743920
SN - 0033-3158
VL - 155
SP - 338
EP - 347
JO - Psychopharmacology
JF - Psychopharmacology
IS - 4
ER -