PMID- 19429089 OWN - NLM STAT- MEDLINE DCOM- 20090715 LR - 20221207 IS - 1872-7972 (Electronic) IS - 0304-3940 (Linking) VI - 454 IP - 3 DP - 2009 May 1 TI - Inhibitory effect of selective serotonin reuptake inhibitors on the vesicular monoamine transporter 2. PG - 229-32 LID - 10.1016/j.neulet.2009.03.049 [doi] AB - 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. FAU - Yasumoto, Satoshi AU - Yasumoto S AD - Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan. FAU - Tamura, Kohei AU - Tamura K FAU - Karasawa, Junichi AU - Karasawa J FAU - Hasegawa, Ryota AU - Hasegawa R FAU - Ikeda, Kazutaka AU - Ikeda K FAU - Yamamoto, Toshifumi AU - Yamamoto T FAU - Yamamoto, Hideko AU - Yamamoto H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090318 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Serotonin Uptake Inhibitors) RN - 0 (Slc18a2 protein, rat) RN - 0 (Vesicular Monoamine Transport Proteins) RN - 01K63SUP8D (Fluoxetine) RN - 41VRH5220H (Paroxetine) RN - 44RAL3456C (Methamphetamine) RN - 8B1QWR724A (Reserpine) RN - J6292F8L3D (Haloperidol) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - O4L1XPO44W (Fluvoxamine) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Dopamine/metabolism MH - Fluoxetine/pharmacology MH - Fluvoxamine/pharmacology MH - Haloperidol/pharmacology MH - Male MH - Methamphetamine/pharmacology MH - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology MH - Paroxetine/pharmacology MH - Rats MH - Rats, Wistar MH - Reserpine/pharmacology MH - Selective Serotonin Reuptake Inhibitors/*pharmacology MH - Synaptic Vesicles/drug effects/metabolism MH - Vesicular Monoamine Transport Proteins/*drug effects/*metabolism EDAT- 2009/05/12 09:00 MHDA- 2009/07/16 09:00 CRDT- 2009/05/12 09:00 PHST- 2008/10/24 00:00 [received] PHST- 2009/03/06 00:00 [revised] PHST- 2009/03/12 00:00 [accepted] PHST- 2009/05/12 09:00 [entrez] PHST- 2009/05/12 09:00 [pubmed] PHST- 2009/07/16 09:00 [medline] AID - S0304-3940(09)00332-2 [pii] AID - 10.1016/j.neulet.2009.03.049 [doi] PST - ppublish SO - Neurosci Lett. 2009 May 1;454(3):229-32. doi: 10.1016/j.neulet.2009.03.049. Epub 2009 Mar 18.