Target Information

Target General Infomation
Target ID
T48873
Former ID
TTDS00118
Target Name
Synaptic vesicle amine transporter
Gene Name
SLC18A2
Synonyms
Monoamine transporter; Solute carrier family 18 member 2; VAT; VMAT; Vesicular Monoamine Transporter ; Vesicular amine transporter; SLC18A2
Target Type
Successful
Disease Alzheimer disease [ICD9: 331; ICD10: G30]
Chorea associated with huntington's disease [ICD10: G10]
High blood pressure [ICD9: 401; ICD10: I10-I16]
Hypertension [ICD9: 401; ICD10: I10-I16]
Huntington's disease; Hyperkinetic movement disorder [ICD9:294.1, 333.4, 333; ICD10: F02.2, G10, G20-G26]
Movement disorder [ICD10: R25]
Substance dependence [ICD10: F10-F19]
Tardive dyskinesia [ICD10: G24]
Function
Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis.
BioChemical Class
Major facilitator superfamily
Target Validation
T48873
UniProt ID
Q05940
Sequence
MALSELALVRWLQESRRSRKLILFIVFLALLLDNMLLTVVVPIIPSYLYSIKHEKNATEI
QTARPVHTASISDSFQSIFSYYDNSTMVTGNATRDLTLHQTATQHMVTNASAVPSDCPSE
DKDLLNENVQVGLLFASKATVQLITNPFIGLLTNRIGYPIPIFAGFCIMFVSTIMFAFSS
SYAFLLIARSLQGIGSSCSSVAGMGMLASVYTDDEERGNVMGIALGGLAMGVLVGPPFGS
VLYEFVGKTAPFLVLAALVLLDGAIQLFVLQPSRVQPESQKGTPLTTLLKDPYILIAAGS
ICFANMGIAMLEPALPIWMMETMCSRKWQLGVAFLPASISYLIGTNIFGILAHKMGRWLC
ALLGMIIVGVSILCIPFAKNIYGLIAPNFGVGFAIGMVDSSMMPIMGYLVDLRHVSVYGS
VYAIADVAFCMGYAIGPSAGGAIAKAIGFPWLMTIIGIIDILFAPLCFFLRSPPAKEEKM
AILMDHNCPIKTKMYTQNNIQSYPIGEDEESESD
Drugs and Mode of Action
Drug(s) Alkavervir Drug Info Approved High blood pressure [551871]
Alseroxylon Drug Info Approved Hypertension [550752]
Deutetrabenazine Drug Info Approved Chorea associated with huntington's disease [889446]
Reserpine Drug Info Approved Hypertension [468055], [538424]
Tetrabenazine Drug Info Approved Huntington's disease; Hyperkinetic movement disorder [468067], [529941], [530894], [532471], [538577], [551871]
Valbenazine Tosylate Drug Info Approved Tardive dyskinesia [889446]
AV 133 Drug Info Phase 3 Alzheimer disease [548627]
NBI-98854 Drug Info Phase 3 Movement disorder [524967], [543251]
Lobeline Drug Info Phase 2 Substance dependence [532434]
Antagonist 3,4-Methylenedioxymethamphetamine Drug Info [551382]
4-Methoxyamphetamine Drug Info [551380]
MMDA Drug Info [551393]
Modulator Alkavervir Drug Info [556264]
Deutetrabenazine Drug Info [556264]
Valbenazine Tosylate Drug Info [556264]
Blocker Alseroxylon Drug Info [536284]
Reserpine Drug Info [537569]
Tetrabenazine Drug Info [537083], [537569]
Enhancer AV 133 Drug Info [532499]
Inhibitor Lobeline Drug Info [531251]
NBI-98854 Drug Info [533314]
[11C]DTBZ Drug Info [543358]
[125I]7-azido-8-iodoketanserine Drug Info [534484]
[3H]TBZOH Drug Info [534267]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Synaptic vesicle cycle
Serotonergic synapse
Dopaminergic synapse
Parkinson&#039
s disease
Cocaine addiction
Amphetamine addiction
Alcoholism
PANTHER Pathway Adrenaline and noradrenaline biosynthesis
5HT1 type receptor mediated signaling pathway
5HT2 type receptor mediated signaling pathway
5HT3 type receptor mediated signaling pathway
5HT4 type receptor mediated signaling pathway
Dopamine receptor mediated signaling pathway
Nicotine pharmacodynamics pathway
CCKR signaling map ST
Reactome Norepinephrine Neurotransmitter Release Cycle
Na+/Cl- dependent neurotransmitter transporters
WikiPathways Dopaminergic Neurogenesis
Synaptic Vesicle Pathway
Neurotransmitter Release Cycle
Nicotine Activity on Dopaminergic Neurons
References
Ref 468055(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4823).
Ref 468067(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4834).
Ref 524967ClinicalTrials.gov (NCT02274558) A Phase 3 Study of NBI-98854 for the Treatment of Tardive Dyskinesia. U.S. National Institutes of Health.
Ref 5299412008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
Ref 530894Role of tetrabenazine for Huntington's disease-associated chorea. Ann Pharmacother. 2010 Jun;44(6):1080-9.
Ref 532434Effects of VMAT2 inhibitors lobeline and GZ-793A on methamphetamine-induced changes in dopamine release, metabolism and synthesis in vivo. J Neurochem. 2013 Oct;127(2):187-98.
Ref 532471The druggable genome: Evaluation of drug targets in clinical trials suggests major shifts in molecular class and indication. Annu Rev Pharmacol Toxicol. 2014;54:9-26.
Ref 538424FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 009838.
Ref 538577FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 021894.
Ref 543251(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8694).
Ref 548627Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027191)
Ref 550752Drug information of Alseroxylon, 2008. eduDrugs.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 889446Drugs@FDA (Edaravone)
Ref 531251Design, synthesis and interaction at the vesicular monoamine transporter-2 of lobeline analogs: potential pharmacotherapies for the treatment of psychostimulant abuse. Curr Top Med Chem. 2011;11(9):1103-27.
Ref 532499Brain imaging of vesicular monoamine transporter type 2 in healthy aging subjects by 18F-FP-(+)-DTBZ PET. PLoS One. 2013 Sep 30;8(9):e75952.
Ref 533314NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study. Mov Disord. 2015 Oct;30(12):1681-7.
Ref 534267Active transport of acetylcholine by the human vesicular acetylcholine transporter. J Biol Chem. 1996 Nov 1;271(44):27229-32.
Ref 534484Peptide mapping of the [125I]Iodoazidoketanserin and [125I]2-N-[(3'-iodo-4'-azidophenyl)propionyl]tetrabenazine binding sites for the synaptic vesicle monoamine transporter. J Biol Chem. 1997 Oct 10;272(41):26049-55.
Ref 536284Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
Ref 53708311C-dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls. J Nucl Med. 2009 Mar;50(3):382-9. Epub 2009 Feb 17.
Ref 537569Dopamine signaling is required for depolarization-induced slow current in cerebellar Purkinje cells. J Neurosci. 2009 Jul 1;29(26):8530-8.
Ref 543358(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1012).
Ref 551380Differential behavioural and neurochemical effects of para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine in the rat. Prog Neuropsychopharmacol Biol Psychiatry. 2000 Aug;24(6):955-77.
Ref 551382The origin of <span class="caps">MDMA</span> (ecstasy) revisited: the true story reconstructed from the original documents. Addiction. 2006 Sep;101(9):1241-5.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

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