Thioridazine

Structural formula
	1: 1 mixture of ( R ) -form (left) and ( S ) -form (right)
General
Non-proprietary name	Thioridazine
other names	( RS ) -10- [2- (1-methylpiperidin-2-yl) ethyl] -2-methylsulfanylphenothiazine ( IUPAC )
Molecular formula	C 21 H 26 N 2 S 2 (thioridazine) ; C 21 H 27 N 2 S 2 Cl ( hydrochloride ) ;
Brief description	white to almost white powder
External identifiers / databases
ECHA InfoCard	100,000,041
PubChem	5452
DrugBank	DB00679
Wikidata	Q58375
Drug information
ATC code	N05 AC02
Drug class	Antipsychotics
properties
Molar mass	370.57 g · mol -1 (thioridazine) ; 407.05 g · mol -1 (hydrochloride) ;
Melting point	72–74 ° C (thioridazine) ; 158-160 ° C (hydrochloride) ;
boiling point	230 ° C (thioridazine, 2.66 Pa)
solubility	almost insoluble in water; Easily soluble in dichloromethane and methanol ; soluble in ethanol ;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 302-315-319-335-410
	P: 261-273-305 + 351 + 338-501
Toxicological data	995 mg kg −1 ( LD 50 , rat , oral , thioridazine) ; 385 mg kg −1 ( LD 50 , mouse , oral , thioridazine) ; 1060 mg kg −1 ( LD 50 , rat , oral , hydrochloride) ; 360 mg kg −1 ( LD 50 , mouse , oral , hydrochloride) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Thioridazine is a drug from the group of neuroleptics used as a sedative and antipsychotic .

The chemical compound belongs to the phenothiazines and is used in the form of the racemate .

Pharmacological properties

Thioridazine shows a strong blockade of

α ₁ adrenoceptors

and a moderate blockage of

Because of its weak neuroleptic potency , it was preferred for sedation .

Quetiapine has a similar spectrum of activity as thioridazine .

Thioridazine also acts as FIASMA (functional inhibitor of acid sphingomyelinase ).

Admission

Thioridazin was patented by Sandoz in 1966 and marketed under the trade name Melleril . The drug is mainly used as a more water-soluble hydrochloride or tartrate .

Due to QTc prolongation (see QT syndrome ), the largest manufacturer Novartis had taken Melleril out of the market in the USA and Europe.

In India, thioridazine has recently been used successfully in several small studies against extremely resistant strains of Mycobacterium tuberculosis (XDR-TB). Larger clinical studies are planned.

unwanted effects

As with other neuroleptics, side effects are manifested by anticholinergic effects.

Trade names

Mellaril , Mellaril-S (USA), Melleril , Melleretten (D, A, CH)

literature

Ernst Mutschler: drug effects. 7th edition. Wissenschaftliche Verlagsgesellschaft, Stuttgart 1996. pp. 143–149.

Individual evidence

↑ ^a ^b ^c ^d ^e data sheet THIORIDAZINE CRS (PDF) at EDQM , accessed on September 15, 2010.
↑ ^a ^b ^c ^d ^e ^f Entry on thioridazine. In: Römpp Online . Georg Thieme Verlag, accessed on September 21, 2011.
↑ ^a ^b Data sheet Thioridazine hydrochloride from Sigma-Aldrich , accessed on April 24, 2011 ( PDF ).
↑ Harald Schmidt (ed.), Founded by Claus-Jürgen Estler: Pharmakologie und Toxikologie, 6th edition. Schattauer, Stuttgart u. New York 2007, p. 225.
↑ Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . 6, No. 8, 2011, p. E23852. doi : 10.1371 / journal.pone.0023852 .
↑ THIORIDAZINE - Withdrawn due to poor benefit / risk profile , WHO Pharmaceuticals Newsletter 2005, No. 01, accessed November 20, 2016.
↑ ZF Udwadia, T. Sen, LM Pinto: Safety and efficacy of thioridazine as salvage therapy in Indian patients with XDR-TB. In: Recent patents on anti-infective drug discovery. Volume 6, Number 2, May 2011, pp. 88-91, PMID 21631417 .
↑ MJ Boeree: Global clinical trials for the treatment of TB with thioridazine. In: Recent patents on anti-infective drug discovery. Volume 6, Number 2, May 2011, pp. 99-103, PMID 21548879 .
↑ Torsten Kratz, Albert Diefenbacher: Psychopharmacotherapy in old age. Avoidance of drug interactions and polypharmacy. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f. (July 22) 2019, pp. 508-517, p. 511.

[Ph._Eur.-1] ↑ ^a ^b ^c ^d ^e data sheet THIORIDAZINE CRS (PDF) at EDQM , accessed on September 15, 2010.

[römpp-2] ↑ ^a ^b ^c ^d ^e ^f Entry on thioridazine. In: Römpp Online . Georg Thieme Verlag, accessed on September 21, 2011.

[Sigma-3] Data sheet Thioridazine hydrochloride from Sigma-Aldrich , accessed on April 24, 2011 ( PDF ).

[4] Harald Schmidt (ed.), Founded by Claus-Jürgen Estler: Pharmakologie und Toxikologie, 6th edition. Schattauer, Stuttgart u. New York 2007, p. 225.

[pmid18504571-5] Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . 6, No. 8, 2011, p. E23852. doi : 10.1371 / journal.pone.0023852 .

[6] THIORIDAZINE - Withdrawn due to poor benefit / risk profile , WHO Pharmaceuticals Newsletter 2005, No. 01, accessed November 20, 2016.

[PMID21631417-7] ZF Udwadia, T. Sen, LM Pinto: Safety and efficacy of thioridazine as salvage therapy in Indian patients with XDR-TB. In: Recent patents on anti-infective drug discovery. Volume 6, Number 2, May 2011, pp. 88-91, PMID 21631417 .

[PMID21548879-8] MJ Boeree: Global clinical trials for the treatment of TB with thioridazine. In: Recent patents on anti-infective drug discovery. Volume 6, Number 2, May 2011, pp. 99-103, PMID 21548879 .

[9] Torsten Kratz, Albert Diefenbacher: Psychopharmacotherapy in old age. Avoidance of drug interactions and polypharmacy. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f. (July 22) 2019, pp. 508-517, p. 511.