Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMYWQ0O)

• Drug Name: Tetrabenazine Drug Info
• Synonyms: Nitoman; Rubigen; Tetrabenazina; Tetrabenazinum; Tetrabenzaine; Tetrabenzine; Xenazine; Tetra Benazin; Nitoman (TN); Ro 1-9569; Tetrabenazina [INN-Spanish]; Tetrabenazine (INN); Tetrabenazine [INN:BAN]; Tetrabenazinum [INN-Latin]; Xenazine (TN); Nitoman, Xenazine, Tetrabenazine; Ro 1-9569/12; 1,3,4,6,7,11b-Hexahydro-3-isobutyl-9,10-dimethoxy-2H-benzo(a)quinolizin-2-one; 1,3,4,6,7,11b-Hexahydro-3-isobutyl-9,10-dimethoxy-2H-benzo[a]quinolizin-2-one; 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-Benzo[a]quinolizin-2-one; 2-Oxo-3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11bH-benzo[a]quinolizine; 2-Oxo-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11-beta-hexahydro-2H-benzoquinolizine; 2-Oxo-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11.beta.-hexahydro-2H-benzoquinolizine; 2H-Benzo(a)quinolizin-2-one, 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-(9CI); 9,10-dimethoxy-3-(2-methylpropyl)-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one; 9,10-dimethoxy-3-(2-methylpropyl)-1,3,4,6,7,11b-hexahydrobenzo[a]quinolizin-2-one

Indication

Disease Entry	ICD 11	Status	REF
Huntington disease	8A01.10	Approved	[1]
Hyperkinetic movement disorder	6B60.8	Approved	[1]

• Therapeutic Class: Nephropathic cystinosis therapy
• Cross-matching ID:
  PubChem CID: 6018
  ChEBI ID: CHEBI:64028
  CAS Number: CAS 718635-93-9
  TTD Drug ID: DMYWQ0O
  VARIDT Drug ID: DR01035
  INTEDE Drug ID: DR1567
  ACDINA Drug ID: D00667

Molecule-Related Drug Atlas

Drug(s) Targeting Synaptic vesicle amine transporter (SLC18A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Deutetrabenazine	DMUPFLI	Huntington disease	8A01.10	Approved	[5]
Reserpine	DM6VM38	Hypertension	BA00-BA04	Approved	[2]
Alseroxylon	DMB47TQ	Hypertension	BA00-BA04	Approved	[6]
Valbenazine Tosylate	DMQSA2V	Tardive dyskinesia	8A02.10	Approved	[5]
Alkavervir	DMB4HFI	High blood pressure	BA00	Approved	[5]
Ingrezza	DMVPLNC	Tardive dyskinesia	8A02.10	Phase 4	[7]
NBI-98854	DMVO1C0	Movement disorder	8A07-8A0Z	Phase 3	[8]
AV 133	DM0EQ9X	Alzheimer disease	8A20	Phase 3	[9]
Lobeline	DMT3KB4	Substance use disorder	6C4Z	Phase 2	[10]
SOM3355	DMKCBSM	Huntington disease	8A01.10	Phase 2	[11]

Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[12]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[13]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[14]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[16]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[17]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[18]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[19]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[20]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[21]

Drug(s) Affected By Synaptic vesicular amine transporter (SLC18A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Norepinephrine	DMOUC09	Alopecia	ED70	Approved	[4]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[4]
Methamphetamine	DMPM4SK	Anxiety		Approved	[22]
Ergotidine	DM78IME	Osteoarthritis	FA00-FA05	Approved	[23]
Haloperidol	DM96SE0	Delirium		Approved	[23]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[24]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[25]
Dextroamphetamine	DMMIHVP	Attention deficit hyperactivity disorder	6A05.Z	Approved	[23]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[26]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Synaptic vesicle amine transporter (SLC18A2)	TTNZRI3	VMAT2_HUMAN	Blocker	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Synaptic vesicular amine transporter (SLC18A2)	OTUOMMM6	VMAT2_HUMAN	Gene/Protein Processing	[4]

References

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• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [7] VMAT2 Inhibitors and the Path to Ingrezza (Valbenazine). Prog Med Chem. 2018;57(1):87-111.
• [8] NBI-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.
• [9] Brain imaging of vesicular monoamine transporter type 2 in healthy aging subjects by 18F-FP-(+)-DTBZ PET. PLoS One. 2013 Sep 30;8(9):e75952.
• [10] Design, 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.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [13] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [14] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [15] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [16] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [17] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [18] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [19] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [20] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [21] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
• [22] Assessing Vesicular Monoamine Transport and Toxicity Using Fluorescent False Neurotransmitters. Chem Res Toxicol. 2021 May 17;34(5):1256-1264. doi: 10.1021/acs.chemrestox.0c00380. Epub 2020 Dec 30.
• [23] Synaptic vesicular monoamine transporter expression: distribution and pharmacologic profile. Brain Res Mol Brain Res. 1994 Mar;22(1-4):219-26. doi: 10.1016/0169-328x(94)90050-7.
• [24] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [25] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [26] Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
• [27] Loss of striatal vesicular monoamine transporter protein (VMAT2) in human cocaine users. Am J Psychiatry. 2003 Jan;160(1):47-55. doi: 10.1176/appi.ajp.160.1.47.