Novel benztropine [3a-(diphenylmethoxy)tropane] analogs as probes for the dopamine transporter.
The design, synthesis and pharmacological evaluation of novel dopamine transporter ligands, based on Benztropine [3a-(diphenylmethoxy) tropane], has been a focus of our research efforts toward the development of novel cocaine-abuse pharmacotherapeutics. Structure-activity relationships at the dopamine transporter, for this series of compounds, have been derived and compared to those of cocaine and GBR 12909. These studies suggest that structurally diverse dopamine uptake inhibitors may access different binding domains on the dopamine transporter. The distinctive behavioral profile displayed in this series of compounds, as compared to cocaine and other dopamine uptake inhibitors, is of particular interest and is proposed to be relevant to the pharmacodynamic and pharmacokinetic properties of this class of tropane-based molecules.
Psychobiology Section, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
A H
AH
Newman
G E
GE
Agoston
D001590:Benztropine / Q000031:analogs & derivatives*; D002352:Carrier Proteins / Q000187:drug effects*; D003042:Cocaine / Q000009:adverse effects; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000209:etiology
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; D001590:Benztropine; C043425:vanoxerine; D003042:Cocaine