Dopamine transport inhibitors based on GBR12909 and benztropine as potential medications to treat cocaine addiction.
The discovery and development of medications to treat addiction and notably, cocaine addiction, have been frustrated by both the complexity of the disorder and the lack of target validation in human subjects. The dopamine transporter has historically been a primary target for cocaine abuse medication development, but addictive liability and other confounds of such inhibitors of dopamine uptake have limited clinical evaluation and validation. Herein we describe efforts to develop analogues of the dopamine uptake inhibitors GBR 12909 and benztropine that show promising profiles in animal models of cocaine abuse that contrast to that of cocaine. Their unique pharmacological profiles have provided important insights into the reinforcing actions of cocaine and we propose that clinical investigation of novel dopamine uptake inhibitors will facilitate the discovery of cocaine-abuse medications.
Rothman
Richard B
RB
Clinical Psychopharmacology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 333 Cassell Dr., Baltimore, MD 21224, USA.
Baumann
Michael H
MH
Prisinzano
Thomas E
TE
Newman
Amy Hauck
AH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001590:Benztropine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D003213:Conditioning, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D001590:Benztropine; C043425:vanoxerine