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

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Book cover Transporters as Targets for Drugs

Part of the book series: Topics in Medicinal Chemistry ((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.

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Author information

Authors and Affiliations

  1. Medications Discovery Research Branch, National Institute on Drug Abuse Intramural ResearchProgram, National Institutes of Health, 21224, Baltimore, MD, USA

    Amy Hauck Newman & Jonathan L. Katz

  2. Medicinal Chemistry Section, NIDA-IRP, NIH, 333 Cassell Dr., 21224, Baltimore, MD, USA

    Amy Hauck Newman

  3. Psychobiology Section, NIDA-IRP, NIH, 5500 Nathan Shock Dr., 21224, Baltimore, MD, USA

    Jonathan L. Katz

Authors
  1. Amy Hauck Newman
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  2. Jonathan L. Katz
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Corresponding author

Correspondence to Amy Hauck Newman .

Editor information

Susan Napier Matilda Bingham

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© 2008 Springer-Verlag Berlin Heidelberg

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Hauck Newman, A., Katz, J.L. (2008). Atypical Dopamine Uptake Inhibitors that Provide Clues About Cocaine's Mechanism at the Dopamine Transporter. In: Napier, S., Bingham, M. (eds) Transporters as Targets for Drugs. Topics in Medicinal Chemistry, vol 4. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7355_2008_027

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