Mechanism of action of cocaine and amphetamine on synaptic terminal of dopamine (DA) neurons. Left: Cocaine inhibits the dopamine transporter (DAT), decreasing.

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Mechanism of action of cocaine and amphetamine on synaptic terminal of dopamine (DA) neurons. Left: Cocaine inhibits the dopamine transporter (DAT), decreasing DA clearance from the synaptic cleft and causing an increase in extracellular DA concentration. Right: Since amphetamine (Amph) is a substrate of the DAT, it competitively inhibits DA transport. In addition, once in the cell, amphetamine interferes with the vesicular monoamine transporter (VMAT) and impedes the filling of synaptic vesicles. As a consequence, vesicles are depleted and cytoplasmic DA increases. This leads to a reversal of DAT direction, strongly increasing nonvesicular release of DA, and further increasing extracellular DA concentrations. Source: Drugs of Abuse, Basic & Clinical Pharmacology, 13e Citation: Katzung BG, Trevor AJ. Basic & Clinical Pharmacology, 13e; 2015 Available at: http://accessmedicine.mhmedical.com/DownloadImage.aspx?image=/data/Books/1193/kat_ch32_f004.png&sec=69108776&BookID=1193&ChapterSecID=69108683&imagename= Accessed: November 11, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved