New insights into the mechanism of action of amphetamines.

Article Details

Citation

Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR

New insights into the mechanism of action of amphetamines.

Annu Rev Pharmacol Toxicol. 2007;47:681-98.

PubMed ID
17209801 [ View in PubMed
]
Abstract

Amphetamine is a psychostimulant commonly used to treat several disorders, including attention deficit, narcolepsy, and obesity. Plasmalemmal and vesicular monoamine transporters, such as the neuronal dopamine transporter and the vesicular monoamine transporter-2, are two of its principal targets. This review focuses on new insights, obtained from both in vivo and in vitro studies, into the molecular mechanisms whereby amphetamine, and the closely related compounds methamphetamine and methylenedioxymethamphetamine, cause monoamine, and particularly dopamine, release. These mechanisms include amphetamine-induced exchange diffusion, reverse transport, and channel-like transport phenomena as well as the weak base properties of amphetamine. Additionally, amphetamine analogs may affect monoamine transporters through phosphorylation, transporter trafficking, and the production of reactive oxygen and nitrogen species. All of these mechanisms have potential implications for both amphetamine- and methamphetamine-induced neurotoxicity, as well as dopaminergic neurodegenerative diseases.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
4-MethoxyamphetamineSodium-dependent dopamine transporterProteinHumans
Yes
Inhibitor
Details
AmphetamineSodium-dependent serotonin transporterProteinHumans
Unknown
Binder
Details
Ephedra sinica rootChromaffin granule amine transporterProteinHumans
Yes
Inhibitor
Details
Ephedra sinica rootSodium-dependent dopamine transporterProteinHumans
Yes
Negative modulator
Details
Ephedra sinica rootSodium-dependent noradrenaline transporterProteinHumans
Yes
Negative modulator
Details
Ephedra sinica rootSodium-dependent serotonin transporterProteinHumans
Yes
Negative modulator
Details
Ephedra sinica rootSynaptic vesicular amine transporterProteinHumans
Yes
Inhibitor
Details
EphedrineSodium-dependent noradrenaline transporterProteinHumans
Unknown
Inverse agonist
Details
MetamfetamineChromaffin granule amine transporterProteinHumans
Yes
Inhibitor
Details
MetamfetamineSodium-dependent dopamine transporterProteinHumans
Yes
Negative modulator
Details
MetamfetamineSodium-dependent noradrenaline transporterProteinHumans
Yes
Negative modulator
Details
MetamfetamineSynaptic vesicular amine transporterProteinHumans
Yes
Inhibitor
Details
MidomafetamineSodium-dependent dopamine transporterProteinHumans
Unknown
Negative modulator
Details
MidomafetamineSodium-dependent noradrenaline transporterProteinHumans
Yes
Negative modulator
Details
MMDA5-hydroxytryptamine receptor 2AProteinHumans
Yes
Agonist
Details
MMDAChromaffin granule amine transporterProteinHumans
Yes
Inhibitor
Details
MMDASodium-dependent dopamine transporterProteinHumans
Yes
Negative modulator
Details
MMDASodium-dependent noradrenaline transporterProteinHumans
Yes
Negative modulator
Details
MMDASodium-dependent serotonin transporterProteinHumans
Yes
Negative modulator
Details
MMDASynaptic vesicular amine transporterProteinHumans
Yes
Inhibitor
Details
Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
EphedrineSynaptic vesicular amine transporterProteinHumans
Unknown
Inhibitor
Details