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Atypical Dopamine Uptake Inhibitors that Provide Clues About Cocaine's Mechanism at the Dopamine Transporter

  • Amy Hauck NewmanEmail author
  • Jonathan L. Katz
Chapter
Part of the Topics in Medicinal Chemistry book series (TMC, volume 4)

Abstract

The dopamine transporter (DAT) has been a primary target for cocaine abuse/addiction medicationdiscovery. However predicted addiction liability and limited clinical evaluation has provided a formidablechallenge for development of these agents for human use. The unique and atypical pharmacological profileof the benztropine (BZT) class of dopamine uptake inhibitors, in preclinical models of cocaine effects andabuse, has encouraged further development of these agents. Moreover, in vivo studies have challenged theoriginal DAT hypothesis and demonstrated that DAT occupancy and subsequent increases in dopamine producedby BZT analogues are significantly delayed and long lasting, as compared to cocaine. These important anddistinctive elements are critical to the lack of abuse liability among BZT analogues, and improve theirpotential for development as treatments for cocaine abuse and possibly other neuropsychiatric disorders.

Addiction medication discovery Benztropine Cocaine Dopamine transporter Dopamine uptake inhibitor 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  1. 1.Medications Discovery Research Branch, National Institute on Drug Abuse Intramural ResearchProgramNational Institutes of HealthBaltimoreUSA
  2. 2.Medicinal Chemistry SectionNIDA-IRP, NIHBaltimoreUSA
  3. 3.Psychobiology SectionNIDA-IRP, NIHBaltimoreUSA

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