Inhibitory effect of selective serotonin reuptake inhibitors on the vesicular monoamine transporter 2.

Article Details

Citation

Yasumoto S, Tamura K, Karasawa J, Hasegawa R, Ikeda K, Yamamoto T, Yamamoto H

Inhibitory effect of selective serotonin reuptake inhibitors on the vesicular monoamine transporter 2.

Neurosci Lett. 2009 May 1;454(3):229-32. doi: 10.1016/j.neulet.2009.03.049. Epub 2009 Mar 18.

PubMed ID
19429089 [ View in PubMed
]
Abstract

The neuronal vesicular monoamine transporter (VMAT2) is the target molecule of action of some psychostimulants, such as methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). The present study examined the effect of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), on VMAT2 activity by measuring adenosine triphosphate-dependent [(3)H]dopamine uptake into synaptic vesicles prepared from rat striatum. SSRIs, fluoxetine, paroxetine, and fluvoxamine, inhibited vesicular [(3)H]dopamine uptake in vitro. The rank order of potency was reserpine>>fluoxetine, paroxetine>fluvoxamine, methamphetamine>MDMA. Moreover, kinetic analysis revealed that inhibition by reserpine, a typical VMAT2 inhibitor, was uncompetitive, decreasing maximum velocity and affinity for dopamine. Inhibition by fluoxetine was noncompetitive, only decreasing maximum velocity for dopamine. These results suggest that fluoxetine inhibited the activity of VMAT2 by a mechanism different from that of reserpine and did not directly interact with the active site of VMAT2.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
MetamfetamineSynaptic vesicular amine transporterProteinHumans
Yes
Inhibitor
Details
Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
EphedrineSynaptic vesicular amine transporterProteinHumans
Unknown
Inhibitor
Details