File:TAAR1 Dopamine vi.svg

English: This is an illustration of a dopamine neuron with colocalized trace amine-associated receptor 1 (TAAR1) and the effects of a TAAR1 agonist (amphetamine or a trace amine like phenethylamine) on dopamine reuptake and effluxion. In technical terms, this is the pharmacodynamics of amphetamine and phenethylamine in this type of neuron.

This model was based upon information from the three following sources:

Wimalasena K (July 2011). "Vesicular monoamine transporters: structure-function, pharmacology, and medicinal chemistry". Med Res Rev 31 (4): 483–519. doi:10.1002/med.20187. PMC 3019297. PMID 20135628 Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468. Eiden LE, Weihe E (January 2011). "VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse". Ann. N. Y. Acad. Sci. 1216: 86–98. doi:10.1111/j.1749-6632.2010.05906.x. PMID 21272013. Supplemental citation with additional coverage of VMAT2 inhibition by phenethylamine:

Offermanns, Stefan; (eds.), Walter Rosenthal (2008). Encyclopedia of Molecular Pharmacology (2nd ed. ed.). Berlin: Springer. pp. 1219–1222. ISBN 3540389164.

In this diagram, amphetamine enters the presynaptic neuron across the neuronal membrane or through the dopamine transporter (DAT). Once inside, it binds to TAAR1 or enters synaptic vesicles through vesicular monoamine transporter 2 (VMAT2). When amphetamine or a trace amine binds to TAAR1, it reduces postsynaptic dopamine neuron firing rate (via mechanisms that are not shown) and triggers protein kinase A (PKA) and protein kinase C (PKC) signaling, resulting in DAT phosphorylation. Phosphorylated DAT then either operates in reverse or withdraws into the presynaptic neuron and ceases transport. When amphetamine or a trace amine enters the synaptic vesicles through VMAT2, dopamine is released into the cytosol (light tan area).