Amphetamines, new psychoactive drugs and the monoamine transporter cycle

Trends Pharmacol Sci. 2015 Jan;36(1):41-50. doi: 10.1016/ Epub 2014 Dec 23.


In monoaminergic neurons, the vesicular transporters and the plasma membrane transporters operate in a relay. Amphetamine and its congeners target this relay to elicit their actions: most amphetamines are substrates, which pervert the relay to elicit efflux of monoamines into the synaptic cleft. However, some amphetamines act as transporter inhibitors. Both compound classes elicit profound psychostimulant effects, which render them liable to recreational abuse. Currently, a surge of new psychoactive substances occurs on a global scale. Chemists bypass drug bans by ingenuous structural variations, resulting in a rich pharmacology. A credible transport model must account for their distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects.

Keywords: addiction; amphetamine; monoamine transporter; psychostimulant; regulation; reverse transport.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amphetamines / chemistry
  • Amphetamines / pharmacology*
  • Animals
  • Biological Transport
  • Humans
  • Plasma Membrane Neurotransmitter Transport Proteins / metabolism*
  • Psychotropic Drugs / chemistry
  • Psychotropic Drugs / pharmacology*


  • Amphetamines
  • Plasma Membrane Neurotransmitter Transport Proteins
  • Psychotropic Drugs