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

Satoshi Yasumoto, Kohei Tamura, Junichi Karasawa, Ryota Hasegawa, Kazutaka Ikeda, Toshifumi Yamamoto, Hideko Yamamoto

Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.

Neuroscience letters 2009 May 1

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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.

Citation

Satoshi Yasumoto, Kohei Tamura, Junichi Karasawa, Ryota Hasegawa, Kazutaka Ikeda, Toshifumi Yamamoto, Hideko Yamamoto. Inhibitory effect of selective serotonin reuptake inhibitors on the vesicular monoamine transporter 2. Neuroscience letters. 2009 May 1;454(3):229-32