Inhibitory effect of selective serotonin reuptake inhibitors on the vesicular monoamine transporter 2
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...
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Published in | Neuroscience letters Vol. 454; no. 3; pp. 229 - 232 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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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 [
3H]dopamine uptake into synaptic vesicles prepared from rat striatum. SSRIs, fluoxetine, paroxetine, and fluvoxamine, inhibited vesicular [
3H]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. |
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AbstractList | 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. 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 [ 3H]dopamine uptake into synaptic vesicles prepared from rat striatum. SSRIs, fluoxetine, paroxetine, and fluvoxamine, inhibited vesicular [ 3H]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. 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. 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 [ super(3)H]dopamine uptake into synaptic vesicles prepared from rat striatum. SSRIs, fluoxetine, paroxetine, and fluvoxamine, inhibited vesicular [ super(3)H]dopamine uptake in vitro. The rank order of potency was reserpine [much greater-than] 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. |
Author | Yamamoto, Toshifumi Ikeda, Kazutaka Yasumoto, Satoshi Hasegawa, Ryota Tamura, Kohei Karasawa, Junichi Yamamoto, Hideko |
Author_xml | – sequence: 1 givenname: Satoshi surname: Yasumoto fullname: Yasumoto, Satoshi organization: Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan – sequence: 2 givenname: Kohei surname: Tamura fullname: Tamura, Kohei organization: Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan – sequence: 3 givenname: Junichi surname: Karasawa fullname: Karasawa, Junichi organization: Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan – sequence: 4 givenname: Ryota surname: Hasegawa fullname: Hasegawa, Ryota organization: Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan – sequence: 5 givenname: Kazutaka surname: Ikeda fullname: Ikeda, Kazutaka organization: Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan – sequence: 6 givenname: Toshifumi surname: Yamamoto fullname: Yamamoto, Toshifumi organization: Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan – sequence: 7 givenname: Hideko surname: Yamamoto fullname: Yamamoto, Hideko email: yamahide@prit.go.jp organization: Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan |
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Keywords | Synaptic vesicle Dopamine Fluoxetine VMAT2 Serotonin Neurotransmitter Catecholamine Reuptake inhibitor Vesicular monoamine transporter |
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SubjectTerms | Animals Biological and medical sciences Dopamine Dopamine - metabolism Fluoxetine Fluoxetine - pharmacology Fluvoxamine - pharmacology Fundamental and applied biological sciences. Psychology Haloperidol - pharmacology Male Methamphetamine - pharmacology N-Methyl-3,4-methylenedioxyamphetamine - pharmacology Paroxetine - pharmacology Rats Rats, Wistar Reserpine - pharmacology Serotonin Uptake Inhibitors - pharmacology Synaptic vesicle Synaptic Vesicles - drug effects Synaptic Vesicles - metabolism Vertebrates: nervous system and sense organs Vesicular Monoamine Transport Proteins - drug effects Vesicular Monoamine Transport Proteins - metabolism VMAT2 |
Title | Inhibitory effect of selective serotonin reuptake inhibitors on the vesicular monoamine transporter 2 |
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