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 inNeuroscience letters Vol. 454; no. 3; pp. 229 - 232
Main Authors Yasumoto, Satoshi, Tamura, Kohei, Karasawa, Junichi, Hasegawa, Ryota, Ikeda, Kazutaka, Yamamoto, Toshifumi, Yamamoto, Hideko
Format Journal Article
LanguageEnglish
Published Shannon Elsevier Ireland Ltd 01.05.2009
Elsevier
Subjects
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
Synaptic vesicle
Dopamine
Fluoxetine
VMAT2
Serotonin
Neurotransmitter
Catecholamine
Reuptake inhibitor
Vesicular monoamine transporter
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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.
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
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  surname: Yamamoto
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  organization: Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
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  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
Language English
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Snippet The neuronal vesicular monoamine transporter (VMAT2) is the target molecule of action of some psychostimulants, such as methamphetamine and...
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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
URI https://dx.doi.org/10.1016/j.neulet.2009.03.049
https://www.ncbi.nlm.nih.gov/pubmed/19429089
https://search.proquest.com/docview/20626979
https://search.proquest.com/docview/67221868
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