pp 1-33 | Cite as

Molecular Mechanisms of Amphetamines

  • Maarten E. A. ReithEmail author
  • Margaret E. Gnegy
Part of the Handbook of Experimental Pharmacology book series


There is a plethora of amphetamine derivatives exerting stimulant, euphoric, anti-fatigue, and hallucinogenic effects; all structural properties allowing these effects are contained within the amphetamine structure. In the first part of this review, the interaction of amphetamine with the dopamine transporter (DAT), crucially involved in its behavioral effects, is covered, as well as the role of dopamine synthesis, the vesicular monoamine transporter VMAT2, and organic cation 3 transporter (OCT3). The second part deals with requirements in amphetamine’s effect on the kinases PKC, CaMKII, and ERK, whereas the third part focuses on where we are in developing anti-amphetamine therapeutics. Thus, treatments are discussed that target DAT, VMAT2, PKC, CaMKII, and OCT3. As is generally true for the development of therapeutics for substance use disorder, there are multiple preclinically promising specific compounds against (meth)amphetamine, for which further development and clinical trials are badly needed.


Amphetamine use disorder Catecholamine Dopamine Monoamine transporter Neurotransmitter release Protein kinase 



The most recent work by the authors described in this review was supported by NIH DA 019676 (MEAR) and R01DA011697 (MEG). We are grateful for the input given on Sect. 4.1 by Kyle C. Schmitt.


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Authors and Affiliations

  1. 1.Department of PsychiatryNew York University School of MedicineNew YorkUSA
  2. 2.Department of PharmacologyUniversity of Michigan School of MedicineAnn ArborUSA

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