Dopamine transporter as target for drug development of cocaine dependence medications.
Because much evidence implicates the dopamine transporter in the reinforcing effects of cocaine, development of potential medications for cocaine dependence has included the dopamine transporter as a target. The present overview covers progress in the drug development area regarding several classes of dopamine uptake inhibitors, with an emphasis on structure-activity relationships that enhance potency and selectivity at transporters for dopamine compared with those for serotonin or norepinephrine. The following categories of compounds are covered: tropane, benztropine, 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR), methylphenidate, mazindol, and phencyclidine analogs. Activity at transporters as well as on behavior is highlighted.
Dutta
Aloke K
AK
Department of Pharmaceutical Sciences, Applebaum College of Pharmacy and Health Science, Wayne State University, 3128 Applebaun Hall, Detroit, MI 48202, USA. adutta@wayne.edu
Zhang
Shijun
S
Kolhatkar
Rohit
R
Reith
Maarten E A
ME
D000818:Animals; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins