Thioridazine hydrochloride Chemical Properties

Melting point:

158-1600C

Boiling point:

230°C (rough estimate)

Density 

1.1227 (rough estimate)

refractive index 

1.5610 (estimate)

storage temp. 

2-8°C

solubility 

H2O: soluble250 mg plus 5 ml of solvent, clear, colorless to faintly yellow

form 

Off-white solid

color 

White to Almost white

Water Solubility 

Soluble in water (75 mM), DMSO (100 mM), chloroform, ethanol, and methanol.

Sensitive 

Light Sensitive & Hygroscopic

λmax

317nm(EtOH)(lit.)

Merck 

14,9359

InChIKey

NZFNXWQNBYZDAQ-UHFFFAOYSA-N

CAS DataBase Reference

130-61-0(CAS DataBase Reference)

NIST Chemistry Reference

Thioridazine hydrochloride(130-61-0)

EPA Substance Registry System

10H-Phenothiazine, 10-[2-(1-methyl-2-piperidinyl)ethyl]-2-(methylthio)-, monohydrochloride (130-61-0)

Safety Information

Hazard Codes 

Xn,N

Risk Statements 

22-36/37/38-50/53

Safety Statements 

26-36-60-61

RIDADR 

UN 3077 9/PG 3

WGK Germany 

3

RTECS 

SP2275000

HazardClass 

9

HS Code 

2934302300

Thioridazine hydrochloride Usage And Synthesis

Chemical Properties

Pale Yellow Solid

Originator

Mellaril,Sandoz,US,1959

Uses

Thioridazine hydrochloride has been used as an intercalating agent for analyzing the integrity of double-stranded DNA (dsDNA) using square-wave voltammetry (SWV) techniques. Thioridazine hydrochloride has also been used as a positive control for the inhibition of hepatic enzyme cytochrome P4502D6 (CYP2D6) in human liver microsomes.

Uses

Dopamine receptor blocker; parent compound of sulforidazine and mesoridazine. Antipsychotic

Uses

Thioridazine HCl is a dopamine receptor blocker and antipsychotic. It is the parent compound of sulforidazine and mesoridazine. This compound has been reported to bind strongly to dopamine receptors on cancer stem cells and cause differentiation leaving normal cells alone (see Can. Chem. News 12 July/August 2012).

Definition

ChEBI: Thioridazine hydrochloride is a hydrochloride. It has a role as a first generation antipsychotic and a geroprotector. It contains a thioridazine.

Manufacturing Process

N-(m-methylmercapto-phenyl)-aniline (MP 59° to 61°C) is prepared by condensing m-methylmercapto-aniline (BP 163° to 165°C/16 mm Hg) with the potassium salt of o-chloro-benzoic acid and decarboxylating the resultant N- (m-methylmercapto-phenyl)-anthranilic acid (MP 139° to 141°C) by heating, and then distilling.
9.87 parts of N-(m-methylmercapto-phenyl)-aniline are heated with 2.93 parts of sulfur and 0.15 part of powdered iodine for 15 minutes in a bath at about 160°C. Upon termination of the ensuing evolution of hydrogen sulfide, animal charcoal is added to the reaction mixture and recrystallization carried out first from 40 parts by volume of chlorobenzene, and then from 25 to 30 parts by volume of benzene at the boiling temperature. The obtained citronyellow 3-methylmercapto-phenothiazine has a MP of 138° to 140°C.
17.82 parts of 2-methylmercapto-phenothiazine, 3.4 parts of finely pulverized sodamide and 80 parts by volume of absolute xylene are heated to boiling for two hours at a bath temperature of 180°C under a reflux condenser and while stirring the reaction mixture. Without interrupting the heating, a solution of 13.2 parts of 2-(N-methyl-piperidyl-2')-1chloro-ethane in 40 parts by volume of absolute xylene is then added dropwise in the course of 1 1/2 hours. After further heating for 3 hours, the reaction mixture is cooled and, after the addition of 5 parts of ammonium chloride, is shaken three times with water, using 25 parts by volume each time. The xylene solution is extracted once with 35 parts by volume of 3 normal acetic acid and then three times, each time with 15 parts by volume of the said acid, after which the acetic acid extract is washed with 60 parts by volume of ether and is then made phenolphthalein-alkaline by means of 25 parts by volume of concentrated aqueous caustic soda solution.
The precipitated oily base is taken up in a total of 100 parts by volume of benzene. The benzene layer, dried over potassium carbonate, is filtered and then evaporated under reduced pressure. The residue from the evaporation is distilled in a high vacuum; after separating a preliminary distillate which passes over up to 228°C under a pressure of 0.92 mm Hg, the principal fraction, 2-methylmercapto-10-[2'-(N-methyl-piperidyl-2'')-ethyl- 1']phenothiazine, which distills over at 228° to 232°C under the lastmentioned pressure, is collected. The analytically pure base has a BP of 230°C/0.02 mm Hg.

Therapeutic Function

Tranquilizer

General Description

Thioridazine hydrochloride,10-[2-(1-methyl-2-piperidyl)ethyl]-2-(methylthio)phenothiazine monohydrochloride (Mellaril), is amember of the piperidine subgroup of the phenothiazines.The drug has a relatively low tendency to produce EPS. Thedrug has high anticholinergic activity, and this activity in thestriatum, counterbalancing a striatal DA block, may be responsiblefor the low EPS. It also has been suggested thatthere may be increased DA receptor selectivity, which may be responsible. The drug has sedative and hypotensive activityin common with chlorpromazine and less antiemeticactivity. At high doses, pigmentary retinopathy has been observed.Its major metabolites include N-demethylated, ringhydroxylated,and S-oxidized products. Thioridazine isprominently converted to the active metabolite mesoridazine(discussed next), which probably contributes to the antipsychoticactivity of thioridazine.

Biological Activity

Dopamine receptor antagonist that displays antipsychotic activity.

Biochem/physiol Actions

D2 dopamine receptor antagonist; phenothazine antipsychotic with reduced extrapyramidal side effects; Ca2+ channel blocker.

storage

Desiccate at RT

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