Tetrabenazine

Tetrabenazine
Clinical data
Trade names	Xenazine, Xentra, Nitoman, others
Other names	Ro-1-9569
AHFS/Drugs.com	Consumer Drug Information
Pregnancy; category	AU: B3; ;
Routes of; administration	By mouth
ATC code	N07XX06 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); BR: Class C1 (Other controlled substances); US: ℞-only;
Pharmacokinetic data
Bioavailability	Low, extensive first pass effect
Protein binding	82–85%
Metabolism	Liver (CYP2D6-mediated)
Elimination half-life	10 hours parent compound (2 to 8 hours active metabolites)
Excretion	Kidney (~75%) and fecal (7–16%)
Identifiers
	IUPAC name (SS,RR)-3-Isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-pyridoisoquinolin-2-one;
CAS Number	58-46-8 ;
PubChem CID	6018;
IUPHAR/BPS	4834;
DrugBank	DB04844 ;
ChemSpider	5796 ;
UNII	Z9O08YRN8O;
KEGG	D08575 ;
ChEMBL	ChEMBL117785 ;
CompTox Dashboard (EPA)	DTXSID0042614 ;
ECHA InfoCard	100.000.348
Chemical and physical data
Formula	C19H27NO3
Molar mass	317.429 g·mol−1
3D model (JSmol)	Interactive image;
Chirality	Racemic mixture
	SMILES O=C3C(CC(C)C)CN2C(c1c(cc(OC)c(OC)c1)CC2)C3;
	InChI InChI=1S/C19H27NO3/c1-12(2)7-14-11-20-6-5-13-8-18(22-3)19(23-4)9-15(13)16(20)10-17(14)21/h8-9,12,14,16H,5-7,10-11H2,1-4H3 ; Key:MKJIEFSOBYUXJB-UHFFFAOYSA-N ;
	(verify)

Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorders. It is sold under the brand names Nitoman and Xenazine among others. On August 15, 2008, the U.S. Food and Drug Administration approved the use of tetrabenazine to treat chorea associated with Huntington's disease. Although other drugs had been used "off label," tetrabenazine was the first approved treatment for Huntington's disease in the U.S.^[5] The compound has been known since the 1950s.

Medical uses

Tetrabenazine is used as a treatment, but not as a cure, for hyperkinetic disorders such as:^[6]^[7]

Huntington's disease – specifically, the chorea associated with it
Tourette syndrome and other tic disorders
Tardive dyskinesia,^[8] a serious and sometimes irreversible side effect of long-term use of many antipsychotics, mainly typical antipsychotics
Hemiballismus, spontaneous flinging limb movements due to contra-lateral subthalamic nucleus damage

Tetrabenazine has been used as an antipsychotic in the treatment of schizophrenia, both in the past^[9]^[10]^[11]^[12]^[13]^[14]^[15]^[16] and in modern times.^[17]^[18]^[19]

Side effects

The most common adverse reactions, which have occurred in at least 10% of subjects in studies and at least 5% greater than in subjects who received placebo, have been: sedation or somnolence, fatigue, insomnia, depression, suicidal thoughts, akathisia, anxiety and nausea.^[4]

Warnings

There is a boxed warning associated with the use of tetrabenazine:^[4]

Increases the risk of depression and suicidal thoughts and behavior in patients with Huntington's disease
Balance risks of depression and suicidality with the clinical need for control of chorea when considering the use of tetrabenazine
Monitor patients for emergence or worsening of depression, suicidality or unusual changes in behavior
Inform patients, caregivers and families of the risk of depression and suicidality and instruct to report behaviours of concern promptly to the treating physician
Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation
Tetrabenazine is contraindicated in patients who are actively suicidal and in patients with untreated or inadequately treated depression

Pharmacology

The precise mechanism of action of tetrabenazine is unknown. Its anti-chorea effect is believed to be due to a reversible depletion of monoamines such as dopamine, serotonin, norepinephrine, and histamine from nerve terminals. Tetrabenazine reversibly inhibits vesicular monoamine transporter 2, resulting in decreased uptake of monoamines into synaptic vesicles, as well as depletion of monoamine storage.^[4]

References

^ "TETRABENAZINE RAN/TETRABENAZINE SUN/TETRABENAZINE RBX (Sun Pharma ANZ Pty Ltd)". Therapeutic Goods Administration.
^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
^ Yero T, Rey JA (December 2008). "Tetrabenazine (Xenazine), An FDA-Approved Treatment Option For Huntington's Disease-Related Chorea". P & T. 33 (12): 690–694. PMC 2730806. PMID 19750050.
^ ^a ^b ^c ^d "Xenazine (tetrabenazine) Tablets, for Oral Use. Full Prescribing Information. Revised: 6/2015" (PDF). H. Lundbeck A/S. Retrieved 9 December 2015.
^ 1st US drug for Huntington's disease wins approval ^{[dead link]}
^ Jankovic J, Beach J (1997). "Long-term effects of tetrabenazine in hyperkinetic movement disorders". Neurology. 48 (2): 358–62. doi:10.1212/wnl.48.2.358. PMID 9040721. S2CID 33577525.
^ Kenney C, Hunter C, Jankovic J (January 2007). "Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders". Movement Disorders. 22 (2): 193–7. doi:10.1002/mds.21222. PMID 17133512. S2CID 22001960.
^ Ondo WG, Hanna PA, Jankovic J (August 1999). "Tetrabenazine treatment for tardive dyskinesia: assessment by randomized videotape protocol". American Journal of Psychiatry. 156 (8): 1279–81. doi:10.1176/ajp.156.8.1279. PMID 10450276. S2CID 40131860.
^ Smith ME (March 1960). "Clinical comparison of tetrabenazine (Ro 1-9569), reserpine and placebo in chronic schizophrenics". Diseases of the Nervous System. 21(3)Suppl (3 Suppl): 120–123. PMID 13832091.
^ Sacerdoti G (1960). "" [First clinical experiences with tetrabenazine]. Rassegna di Studi Psichiatrici (in Italian). 49: 450–460. PMID 13745210.
^ Schmitt W (July 1960). "" [On the pharmacotherapy of psychoses: clinical research on tetrabenazine]. Psychiatria et Neurologia (in German). 140: 23–29. doi:10.1159/000131224. PMID 13748124.
^ Ashcroft GW, Macdougall EJ, Barker PA (March 1961). "A comparison of tetrabenazine and chlorpromazine in chronic schizophrenia". The Journal of Mental Science. 107 (447): 287–293. doi:10.1192/bjp.107.447.287. PMID 13684728.
^ Burckard E, Medhaoui M, Montigneaux P, Pfitzenmeyer J, Pfitzenmeyer H, Schaetzel JC, et al. (January 1962). "" [Clinical, biological and electroencephalographic study of the action of tetrabenazine (Ro 956) in various chronic psychoses]. Annales Médico-Psychologiques (in French). 120 (1): 115–119. PMID 13874731.
^ Kammerer T, Singer L, Geissmann P, Wetta JM (January 1962). "" [Use of a new neuroleptic: tetrabenazine. Clinical, biological and electroencephalographic results]. Annales Médico-Psychologiques (in French). 120 (1): 106–115. PMID 14453492.
^ Lingjaerde O (1963). "Tetrabenazine (Nitoman) in the treatment of psychoses. With a discussion on the central mode of action of tetrabenazine and reserpine". Acta Psychiatrica Scandinavica. 39: SUPPL170:1–SUPPL17109. PMID 14081399.
^ Matsumoto Y, Totsuka S, Kato M, Inoue M, Okagami K (July 1966). "". Nihon Rinsho. Japanese Journal of Clinical Medicine (in Japanese). 24 (7): 1360–1364. PMID 6007641.
^ Malik A, Balkoski V (November 2007). "Neurotransmitter depleter tetrabenazine; potential candidate for schizophrenia treatment?". Schizophrenia Research. 96 (1–3): 267–268. doi:10.1016/j.schres.2007.07.010. PMID 17683910. S2CID 39312847.
^ Remington G, Kapur S, Foussias G, Agid O, Mann S, Borlido C, et al. (February 2012). "Tetrabenazine augmentation in treatment-resistant schizophrenia: a 12-week, double-blind, placebo-controlled trial". Journal of Clinical Psychopharmacology. 32 (1): 95–99. doi:10.1097/JCP.0b013e31823f913e. PMID 22198452. S2CID 2649261.
^ Kaur N, Kumar P, Jamwal S, Deshmukh R, Gauttam V (September 2016). "Tetrabenazine: Spotlight on Drug Review". Annals of Neurosciences. 23 (3): 176–185. doi:10.1159/000449184. PMC 5043267. PMID 27721587.

External links

Xenazine prescribing information FDA Archived 2017-02-16 at the Wayback Machine
NIMH Repository data sheet
"Tetrabenazine" from HOPES: Huntington's Disease Outreach Project for Education at Stanford
Detailed monograph on tetrabenazine on rxmed.com
Information on tetrabenazine from netdoctor.co.uk

Zdroj:https://en.wikipedia.org?pojem=Tetrabenazine
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[1] "TETRABENAZINE RAN/TETRABENAZINE SUN/TETRABENAZINE RBX (Sun Pharma ANZ Pty Ltd)". Therapeutic Goods Administration.

[2] Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.

[hl-3] Yero T, Rey JA (December 2008). "Tetrabenazine (Xenazine), An FDA-Approved Treatment Option For Huntington's Disease-Related Chorea". P & T. 33 (12): 690–694. PMC 2730806. PMID 19750050.

[PI-4] "Xenazine (tetrabenazine) Tablets, for Oral Use. Full Prescribing Information. Revised: 6/2015" (PDF). H. Lundbeck A/S. Retrieved 9 December 2015.

[5] 1st US drug for Huntington's disease wins approval ^{[dead link]}

[JankovicHyperkinectic-6] Jankovic J, Beach J (1997). "Long-term effects of tetrabenazine in hyperkinetic movement disorders". Neurology. 48 (2): 358–62. doi:10.1212/wnl.48.2.358. PMID 9040721. S2CID 33577525.

[pmid17133512-7] Kenney C, Hunter C, Jankovic J (January 2007). "Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders". Movement Disorders. 22 (2): 193–7. doi:10.1002/mds.21222. PMID 17133512. S2CID 22001960.

[pmid10450276-8] Ondo WG, Hanna PA, Jankovic J (August 1999). "Tetrabenazine treatment for tardive dyskinesia: assessment by randomized videotape protocol". American Journal of Psychiatry. 156 (8): 1279–81. doi:10.1176/ajp.156.8.1279. PMID 10450276. S2CID 40131860.

[pmid13832091-9] Smith ME (March 1960). "Clinical comparison of tetrabenazine (Ro 1-9569), reserpine and placebo in chronic schizophrenics". Diseases of the Nervous System. 21(3)Suppl (3 Suppl): 120–123. PMID 13832091.

[pmid13745210-10] Sacerdoti G (1960). "" [First clinical experiences with tetrabenazine]. Rassegna di Studi Psichiatrici (in Italian). 49: 450–460. PMID 13745210.

[pmid13748124-11] Schmitt W (July 1960). "" [On the pharmacotherapy of psychoses: clinical research on tetrabenazine]. Psychiatria et Neurologia (in German). 140: 23–29. doi:10.1159/000131224. PMID 13748124.

[pmid13684728-12] Ashcroft GW, Macdougall EJ, Barker PA (March 1961). "A comparison of tetrabenazine and chlorpromazine in chronic schizophrenia". The Journal of Mental Science. 107 (447): 287–293. doi:10.1192/bjp.107.447.287. PMID 13684728.

[pmid13874731-13] Burckard E, Medhaoui M, Montigneaux P, Pfitzenmeyer J, Pfitzenmeyer H, Schaetzel JC, et al. (January 1962). "" [Clinical, biological and electroencephalographic study of the action of tetrabenazine (Ro 956) in various chronic psychoses]. Annales Médico-Psychologiques (in French). 120 (1): 115–119. PMID 13874731.

[pmid14453492-14] Kammerer T, Singer L, Geissmann P, Wetta JM (January 1962). "" [Use of a new neuroleptic: tetrabenazine. Clinical, biological and electroencephalographic results]. Annales Médico-Psychologiques (in French). 120 (1): 106–115. PMID 14453492.

[pmid14081399-15] Lingjaerde O (1963). "Tetrabenazine (Nitoman) in the treatment of psychoses. With a discussion on the central mode of action of tetrabenazine and reserpine". Acta Psychiatrica Scandinavica. 39: SUPPL170:1–SUPPL17109. PMID 14081399.

[pmid6007641-16] Matsumoto Y, Totsuka S, Kato M, Inoue M, Okagami K (July 1966). "". Nihon Rinsho. Japanese Journal of Clinical Medicine (in Japanese). 24 (7): 1360–1364. PMID 6007641.

[pmid17683910-17] Malik A, Balkoski V (November 2007). "Neurotransmitter depleter tetrabenazine; potential candidate for schizophrenia treatment?". Schizophrenia Research. 96 (1–3): 267–268. doi:10.1016/j.schres.2007.07.010. PMID 17683910. S2CID 39312847.

[pmid22198452-18] Remington G, Kapur S, Foussias G, Agid O, Mann S, Borlido C, et al. (February 2012). "Tetrabenazine augmentation in treatment-resistant schizophrenia: a 12-week, double-blind, placebo-controlled trial". Journal of Clinical Psychopharmacology. 32 (1): 95–99. doi:10.1097/JCP.0b013e31823f913e. PMID 22198452. S2CID 2649261.

[pmid27721587-19] Kaur N, Kumar P, Jamwal S, Deshmukh R, Gauttam V (September 2016). "Tetrabenazine: Spotlight on Drug Review". Annals of Neurosciences. 23 (3): 176–185. doi:10.1159/000449184. PMC 5043267. PMID 27721587.

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v t e Antipsychotics (N05A)
Typical	Butyrophenones: Benperidol Bromperidol Bromperidol decanoate Droperidol Haloperidol^# Haloperidol decanoate Moperone Pipamperone Spiperone Timiperone Trifluperidol Diphenylbutylpiperidines: Fluspirilene Penfluridol Pimozide Phenothiazines: Acepromazine Acetophenazine Butaperazine Carphenazine (carfenazine)^‡ Chlorpromazine Cyamemazine Dixyrazine Fluphenazine Fluphenazine decanoate Fluphenazine enanthate Levomepromazine (methotrimeprazine) Mesoridazine Perazine Periciazine Perphenazine BL-1020 Perphenazine decanoate Perphenazine enanthate Piperacetazine Pipotiazine Pipotiazine palmitate Pipotiazine undecylenate Prochlorperazine Promazine Sulforidazine Thiopropazate Thioproperazine Thioridazine Trifluoperazine Triflupromazine Thioxanthenes: Chlorprothixene Clopenthixol Clopenthixol decanoate Flupentixol Flupentixol decanoate Tiotixene (thiothixene) Zuclopenthixol Zuclopenthixol acetate Zuclopenthixol decanoate
Disputed	Benzamides: Amisulpride Levosulpiride Nemonapride Remoxipride^‡ Sulpiride Sultopride Tiapride Veralipride^‡ Butyrophenones: Melperone Tricyclics: Carpipramine Clocapramine Clorotepine Clotiapine Loxapine Mosapramine Oxyprothepin decanoate Others: Molindone
Atypical	Benzisoxazole/benzisothiazoles: Iloperidone Lurasidone Paliperidone Paliperidone palmitate Perospirone Risperidone^# Ziprasidone Butyrophenones: Lumateperone Phenylpiperazines/quinolinones: Aripiprazole Aripiprazole lauroxil Brilaroxazine^† Brexpiprazole Cariprazine Tricyclics: Asenapine Clozapine^# Olanzapine (+samidorphan) Quetiapine Zotepine Others: Blonanserin Pimavanserin Sertindole
Others	Monoamine-depleting agents: Oxypertine Reserpine Tetrabenazine Others/unknown: Azacyclonol
^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III

v t e Other nervous system drugs (N07X)
Stroke	Tirilazad
ALS	Arimoclomol^§ Mecasermin rinfabate^† Riluzole Xaliproden
Other	Amifampridine Edaravone Eplontersen Fampridine Hydroxybutyric acid Inotersen Laquinimod Patisiran Pitolisant Sodium oxybate Sodium phenylbutyrate/ursodoxicoltaurine Tafamidis Tofersen Troriluzole Vutrisiran hyperkinesis Deutetrabenazine Tetrabenazine Valbenazine
^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III