Tetrabenazine

Structural formula
	( R , R ) -isomer (top) and ( S , S ) -isomer (bottom)
General
Non-proprietary name	Tetrabenazine
other names	( RR , SS ) -1,3,4,6,7,11 b -hexahydro-9,10-dimethoxy-3- (2-methylpropyl) -2 H -benzo [ a ] quinoline
Molecular formula	C 19 H 27 NO 3 (tetrabenazine) ; C 19 H 27 NO 3 HCl (tetrabenazine hydrochloride ) ;
External identifiers / databases
EC number	200-383-6
ECHA InfoCard	100,000,348
PubChem	6018
ChemSpider	5796
DrugBank	DB04844
Wikidata	Q413050
Drug information
ATC code	N07 XX06
properties
Molar mass	317.43 g · mol -1 (tetrabenazine)
Melting point	125–126 ° C (tetrabenazine) ; 208–210 ° C (tetrabenazine hydrochloride) ;
solubility	almost insoluble in cold water (tetrabenazine hydrochloride) ; soluble in DMSO ; soluble in hot water, insoluble in acetone (tetrabenazine) ; soluble in ethanol , chloroform , tert-butyl methyl ether and diethyl ether .;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302
	P: no P-phrases
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Tetrabenazine is a drug that has been approved in Germany since 2007 and in Austria since 2010 for the treatment of Huntington's disease and moderate to severe tardive dyskinesia , and was previously prescribed as a so-called orphan drug for the treatment of these and a few other rare movement disorders or will. In Germany , Denmark and Canada , it is marketed under the brand name Nitoman , Switzerland Xenazine marketed. It was developed in the 1950s. It works by promoting the early metabolic breakdown of the neurotransmitter dopamine . More precisely, it empties the presynaptic dopamine stores.

Clinical effect

Tetrabenazine is used to reduce hyperkinesis (especially chorea and dystonia ). Above all, there are:

Chorea huntington
Tourette syndrome
Tardive dyskinesia ( tardive dyskinesia )
Hemiballism

The dose setting should be made slowly and gradually. Concomitant use of MAO inhibitors is contraindicated .

pharmacology

Pharmacodynamics

Tetrabenazine (abbreviation TBZ) acts as a potent VMAT inhibitor. Its ability to deplete the dopamine resources in the CNS and thus reduce its availability as a neurotransmitter in the synaptic gap is of clinical importance . In its VMAT-inhibiting property, TBZ is similar to reserpine , although the mechanism of action does not seem to be identical in detail. The stereoisomer with the (3 R , 11b R ) configuration has the strongest VMAT affinity . In addition, TBZ acts as an antagonist of dopamine receptors . ¹¹ C -labelled TBZ can be used as PET - Radioligand be used.

Pharmacokinetics

TBZ is subject to a strong first pass effect . The main active metabolite is the hydroxy analogue dihydrotetrabenazine (DTBZ).

Derivatives

In March 2017, the FDA approved deuterated tetrabenazine ( Deutetrabenazine ) from Teva . This has the same properties except for a prolonged effectiveness.

Trade names

Monopreparations

Nitoman, Dystardis (D), Xenazine (CH), Tetmodis (A)

Individual evidence

↑ ^a ^b The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 1580, ISBN 978-0-911910-00-1 .
↑ ^a ^b ^c ^d Tetrabenazine data sheet from Sigma-Aldrich , accessed on October 23, 2016 ( PDF ).

↑ Orphan: Tetrabenazine Tablets ( Memento from January 25, 2014 in the Internet Archive ) (PDF file; 111 kB).

↑ MHRA: Public Assessment Report (PDF file; 541 kB).

↑ C. Kenney, J. Jankovic: Tetrabenazine in the treatment of hyperkinetic movement disorders . In: Expert Review of Neurotherapeutics . tape 6 , no. 1 , 2006, p. 7-17 , doi : 10.1586 / 14737175.6.1.7 , PMID 16466307 .

↑ ^a ^b ^c Guangrong Zheng, Linda P. Dwoskin, Peter A. Crooks: Vesicular monoamine transporter 2: Role as a novel target for drug development . In: AAPS Journal . tape 8 , no. 4 , 2006, p. E682 – E692 , doi : 10.1208 / aapsj080478 , PMID 17233532 , PMC 2751365 (free full text).

↑ DESchwartz, H. Bruderer, J. Rieder, A. Brossi: Metabolic studies of tetrabenazine, a psychotropic drug in animals and man . In: Biochemical Pharmacology . tape 15 , no. 5 , 1966, pp. 645-655 , doi : 10.1016 / 0006-2952 (66) 90031-1 .

↑ Derek Lowe: The First Deuterated Drug Arrives . In: In the Pipeline (Science) . April 4, 2017 ( online ).

[MerckIndex-1] The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 1580, ISBN 978-0-911910-00-1 .

[sigma-2] Tetrabenazine data sheet from Sigma-Aldrich , accessed on October 23, 2016 ( PDF ).

[3] Orphan: Tetrabenazine Tablets ( Memento from January 25, 2014 in the Internet Archive ) (PDF file; 111 kB).

[4] MHRA: Public Assessment Report (PDF file; 541 kB).

[5] C. Kenney, J. Jankovic: Tetrabenazine in the treatment of hyperkinetic movement disorders . In: Expert Review of Neurotherapeutics . tape 6 , no. 1 , 2006, p. 7-17 , doi : 10.1586 / 14737175.6.1.7 , PMID 16466307 .

[GZ_2006-6] Guangrong Zheng, Linda P. Dwoskin, Peter A. Crooks: Vesicular monoamine transporter 2: Role as a novel target for drug development . In: AAPS Journal . tape 8 , no. 4 , 2006, p. E682 – E692 , doi : 10.1208 / aapsj080478 , PMID 17233532 , PMC 2751365 (free full text).

[7] DESchwartz, H. Bruderer, J. Rieder, A. Brossi: Metabolic studies of tetrabenazine, a psychotropic drug in animals and man . In: Biochemical Pharmacology . tape 15 , no. 5 , 1966, pp. 645-655 , doi : 10.1016 / 0006-2952 (66) 90031-1 .

[8] Derek Lowe: The First Deuterated Drug Arrives . In: In the Pipeline (Science) . April 4, 2017 ( online ).