Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI0C7RJO8)
  Drug Name Tetrabenazine Drug Info Amisulpride Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Nephropathic Cystinosis Therapy Antipsychotic Agents
  Structure

 Mechanism of Tetrabenazine-Amisulpride Interaction (Severity Level: Major)
     Additive antidopaminergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tetrabenazine Amisulpride
      Mechanism 1 Antidopaminergic effects
Synaptic vesicular amine transporter  Inhibitor 		Antidopaminergic effects
Dopamine receptor  Antagonist
      Key Mechanism Factor 1
Factor Name Synaptic vesicle amine transporter
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Structure Sequence
MALSELALVRWLQESRRSRKLILFIVFLALLLDNMLLTVVVPIIPSYLYSIKHEKNATEIQTARPVHTASISDSFQSIFSYYDNSTMVTGNATRDLTLHQTATQHMVTNASAVPSDCPSEDKDLLNENVQVGLLFASKATVQLITNPFIGLLTNRIGYPIPIFAGFCIMFVSTIMFAFSSSYAFLLIARSLQGIGSSCSSVAGMGMLASVYTDDEERGNVMGIALGGLAMGVLVGPPFGSVLYEFVGKTAPFLVLAALVLLDGAIQLFVLQPSRVQPESQKGTPLTTLLKDPYILIAAGSICFANMGIAMLEPALPIWMMETMCSRKWQLGVAFLPASISYLIGTNIFGILAHKMGRWLCALLGMIIVGVSILCIPFAKNIYGLIAPNFGVGFAIGMVDSSMMPIMGYLVDLRHVSVYGSVYAIADVAFCMGYAIGPSAGGAIAKAIGFPWLMTIIGIIDILFAPLCFFLRSPPAKEEKMAILMDHNCPIKTKMYTQNNIQSYPIGEDEESESD
Gene Name SLC18A2
Uniprot ID VMAT2_HUMAN
KEGG Pathway hsa:6571
Protein Family Major facilitator superfamily
Protein Function
Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles (PubMed:23363473). Requisite for vesicular amine storage prior to secretion via exocytosis.
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      Key Mechanism Factor 2
Factor Name Dopamine receptor Structure Sequence
Protein Family G-protein coupled receptor 1 family
Protein Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
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      Mechanism Description
  • Additive antidopaminergic effects by the combination of Tetrabenazine and Amisulpride 
     Increased risk of prolong QT interval Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tetrabenazine Amisulpride
      Mechanism 2 Prolong QT interval Prolong QT interval
      Key Mechanism Factor 3
Factor Name QT interval
Factor Description Long QT syndrome is a heart signaling disorder that can cause a fast, chaotic heartbeat (arrhythmia). Many people may not exhibit symptoms, and usually the condition is detected during routine medical tests. In others, the most common symptoms include: sudden fainting, palpitations, dizziness, seizures, sudden death.
      Mechanism Description
  • Increased risk of prolong QT interval by the combination of Tetrabenazine and Amisulpride 

Recommended Action
      Management The use of tetrabenazine in combination with neuroleptic agents or other dopamine antagonists should preferably be avoided. When coadministration is required, patients should be instructed to notify their physician if they experience extrapyramidal symptoms such as bradykinesia, hypertonia, rigidity, restlessness, and dysphagia. Clinicians, caregivers, and family members should be apprised of the risk of neuroleptic malignant syndrome and be alert to potential signs and symptoms such as mental status changes (e.g., mutism, catatonia, stupor, coma, agitation, confusion, hallucinations, delusions), autonomic instability, restlessness, rigidity, ataxia, myoclonus, hyperreflexia, tremors, diaphoresis, elevated creatine phosphokinase levels, and hyperpyrexia. Patients should seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.

References
1 Burke RE, Fahn S, Mayeux R, Weinberg H, Louis K, Willner JH "Neuroleptic malignant syndrome caused by dopamine-depleting drugs in a patient with Huntington disease." Neurology 31 (1981): 1022-5. [PMID: 6115336]
2 Login IS, Cronin MJ, MacLeod RM "Neuroleptic malignant syndrome caused by dopamine depleting drugs." Neurology 32 (1982): 1022-5. [PMID: 6119652]
3 Mateo D, Munoz-Blanco JL, Gimenez-Roldan S "Neuroleptic malignant syndrome related to tetrabenazine introduction and haloperidol discontinuation in Huntington's disease." Clin Neuropharmacol 15 (1992): 63-8. [PMID: 1533561]
4 Moss JH, Stewart DE "Iatrogenic parkinsonism in Huntington's chorea." Can J Psychiatry 31 (1986): 865-6. [PMID: 2948633]
5 Ossemann M, Sindic CJ, Laterre C "Tetrabenazine as a cause of neuroleptic malignant syndrome." Mov Disord 11 (1996): 95. [PMID: 8771075]
6 Petzinger GM, Bressman SB "A case of tetrabenazine-induced neuroleptic malignant syndrome after prolonged treatment." Mov Disord 12 (1997): 246-8. [PMID: 9087987]
7 Product Information. Nitoman (tetrabenazine). Cambridge Laboratories Ltd, Wallsend, Tyne & Wear, .
8 Product Information. Xenazine (tetrabenazine). Prestwick Pharmaceuticals Inc, Washington DC, VA.
9 Stevens E, Roman A, Houa M, Razavi D, Jaspar N "Severe hyperthermia during tetrabenazine therapy for tardive dyskenesia." Intensive Care Med 24 (1998): 369-71. [PMID: 9609418]