Thiethylperazine dimaleate

Names

[ Name ]:
Thiethylperazine dimaleate

[Synonym ]:
2-butenedioate
torecandimaleate
2-(Ethylsulfanyl)-10-[3-(4-methylpiperazin-1-yl)propyl]-10H-phenothiazine (2Z)-but-2-enedioate (1:2)
Thiethylperazinbishydrogenmaleat
THIETHYLPERAZINE MALEATE (200 MG)
torecanmaleate
torecanbimaleate
thiethylperazine dimaleate
10H-Phenothiazine, 2-(ethylthio)-10-[3-(4-methyl-1-piperazinyl)propyl]-, (2Z)-2-butenedioate (1:2)
torecan
toresten
tresten
2-(Ethylsulfanyl)-10-[3-(4-methyl-1-piperazinyl)propyl]-10H-phenothiazine (2Z)-2-butenedioate (1:2)
gs-95

Biological Activity

[Description]:

Thiethylperazine dimaleate is a phenothiazine derivate, and an orally active dopamine D2-receptor and histamine H1-receptor antagonist. Thiethylperazine dimaleate is also a slective ABCC1activator that reduces amyloid-β (Aβ) load in mice. Thiethylperazine dimaleate has anti-emetic, antipsychotic and antimicrobial effects[1][2][3].

[Related Catalog]:

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Infection

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> Histamine Receptor

Signaling Pathways >> Anti-infection >> Bacterial

[Target]

Dopamine D2-receptor[1] Histamine H1-receptor[1] ABCC1[2] Enterococcus faecalis[3]

[In Vitro]

Thiethylperazine could enhance the antibiotic (Vancomycin) activity at a concentration as low as 2 μg/mL. Thiethylperazine inhibits Vancomycin-sensitive E. faecalis ATCC 29212, Vancomycin-resistant E. faecalis ATCC 51299 and vancomycin-resistant E. faecalis (VREF) isolates with MIC values of 8 μg/mL, 16 μg/mL and 8 μg/mL, respectively[3].

[In Vivo]

Thiethylperazine (3 mg/kg; intramuscular injection; twice daily; for 30 days; young APP/PS1 mice) treatment significantly reduces Aβ42 levels in APP/PS1 mice[2]. Animal Model: Young Aβ precursor protein (APPswe) and mutant presenilin-1 (PS1) (APP/PS1) mice[2] Dosage: 3 mg/kg Administration: Intramuscular injection; twice daily; for 30 days Result: Significantly reduced Aβ42 levels in APP/PS1 mice.

[References]

[1]. Czeizel AE, et al. Case-control study of teratogenic potential of thiethylperazine, an anti-emetic drug. BJOG. 2003 May;110(5):497-9.

[2]. Krohn M, et al. Cerebral amyloid-β proteostasis is regulated by the membrane transport protein ABCC1 in mice. J Clin Invest. 2011 Oct;121(10):3924-31.

[3]. Rahbar M, et al. Enhancement of vancomycin activity by phenothiazines against vancomycin-resistant Enterococcus faecium in vitro. Basic Clin Pharmacol Toxicol. 2010 Aug;107(2):676-9.

Chemical & Physical Properties

[ Density]:
1.24g/cm3

[ Boiling Point ]:
559.8ºC at 760 mmHg

[ Melting Point ]:
62-64ºC

[ Molecular Formula ]:
C₃₀H₃₇N₃O₈S₂

[ Molecular Weight ]:
631.760

[ Flash Point ]:
292.4ºC

[ Exact Mass ]:
631.202209

[ PSA ]:
209.52000

[ LogP ]:
4.40320

[ Vapour Pressure ]:
1.46E-12mmHg at 25°C

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: SP0350000

CAS REGISTRY NUMBER :: 1179-69-7

LAST UPDATED :: 199504

DATA ITEMS CITED :: 8

MOLECULAR FORMULA :: C22-H29-N3-S2.2C4-H4-O4

MOLECULAR WEIGHT :: 631.82

WISWESSER LINE NOTATION :: T C666 BN ISJ ES2 B3- AT6N DNTJ D1 &OV1U1VO

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1260 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,51,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 90 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,51,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 680 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,51,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 217 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: MEXPAG Medicina Experimentalis. (Basel, Switzerland) V.1-11, 1959-64; V.18-19, 1968-69. For publisher information, see JNMDBO. Volume(issue)/page/year: 4,145,1961

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 93 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: MEXPAG Medicina Experimentalis. (Basel, Switzerland) V.1-11, 1959-64; V.18-19, 1968-69. For publisher information, see JNMDBO. Volume(issue)/page/year: 4,145,1961

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 1050 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,51,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 27 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,51,1972 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5553 No. of Facilities: 23 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 722 (estimated) No. of Female Employees: 377 (estimated)

Safety Information

[ Hazard Codes ]:
Xi