Clemastine fumarate

Names

[ Name ]:
Clemastine fumarate

[Synonym ]:
(+)-2-[2-[(p-Chloro-α-methyl-α-phenylbenzyl)oxy]ethyl]-1-methylpyrrolidine fumarate salt
(2R)-2-{2-[1-(4-Chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine (2E)-2-butenedioate (1:1)
acide (2E)-but-2-ènedioïque - (2R)-2-{2-[(1R)-1-(4-chlorophényl)-1-phényléthoxy]éthyl}-1-méthylpyrrolidine (1:1)
Pyrrolidine, 2-[2-[1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1-methyl-, (2R)-, (2E)-2-butenedioate (1:1)
(2E)-But-2-endisäure--(2R)-2-{2-[(1R)-1-(4-chlorphenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidin(1:1)
Tavist,Agasten
MFCD00137486
(2R)-2-{2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine (2E)-but-2-enedioate
EINECS 239-055-2
Clemastine fumarate
Pyrrolidine (2-[2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1-methyl
Clemastine fumarate salt
(+)-(2R)-2-(2-(((R)-p-Chloro-a-methyl-a-phenylbenzyl)oxy)ethyl)-1-methylpyrrolidine Fumarate (1:1)
(2R)-2-{2-[(1R)-1-(4-Chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine (2E)-but-2-enedioate (1:1)

Biological Activity

[Description]:

Clemastine Fumarate is a selective histamine H1 receptor antagonist with IC50 of 3 nM.Target: Histamine H1 ReceptorClemastine Fumarate inhibits histamine induced rise in [Ca2+]i in HL-60 cells with an IC50 of 3 nM as compared with that of chlorpheniramine or diphenhydramine with IC50 values of 20 nM and 100 nM, respectively [1]. Clemastine showed a first-pass reduction in the extent of absorption, with oral bioavailability calculated as 39.2 +/- 12.4%. Extravascular distribution of drug was suggested by the high volume of distribution (799 +/- 315 L) and low Cmax (0.577 +/- 0.252 ng/mL/mg) observed at 4.77 +/- 2.26 hours after administration, and by the biphasic decline in plasma concentration. The terminal elimination half-life (t1/2) of clemastine was 21.3 +/- 11.6 hours. Steady-state concentrations of clemastine were consistent with linear pharmacokinetic processes, and clearance was unaffected by age in the range studied, or by race [2].

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

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

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Neurological Disease

[References]

[1]. Seifert, R., et al., Histamine increases cytosolic Ca2+ in dibutyryl-cAMP-differentiated HL-60 cells via H1 receptors and is an incomplete secretagogue. Mol Pharmacol, 1992. 42(2): p. 227-34.

[2]. Schran, H.F., et al., The pharmacokinetics and bioavailability of clemastine and phenylpropanolamine in single-component and combination formulations. J Clin Pharmacol, 1996. 36(10): p. 911-22.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.097 g/cm3

[ Boiling Point ]:
116 °C / 24mmHg

[ Melting Point ]:
61 °C

[ Molecular Formula ]:
C₂₅H₃₀ClNO₅

[ Molecular Weight ]:
459.962

[ Flash Point ]:
211ºC

[ Exact Mass ]:
459.181244

[ PSA ]:
87.07000

[ LogP ]:
4.75410

[ Vapour Pressure ]:
1.94E-07mmHg at 25°C

[ Index of Refraction ]:
1.553

[ Storage condition ]:
Store at RT

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UY0704600

CAS REGISTRY NUMBER :: 14976-57-9

LAST UPDATED :: 199203

DATA ITEMS CITED :: 8

MOLECULAR FORMULA :: C21-H26-Cl-N-O.C4-H4-O4

MOLECULAR WEIGHT :: 460.01

WISWESSER LINE NOTATION :: T5NTJ A1 B2OX1&R&R DG &QV1U1VQ -T

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 :: 3550 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - excitement Behavioral - changes in motor activity (specific assay)

REFERENCE :: BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 106,467,1967

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 82 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - excitement Behavioral - changes in motor activity (specific assay)

REFERENCE :: BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 106,467,1967

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 730 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - excitement Behavioral - changes in motor activity (specific assay)

REFERENCE :: BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 106,467,1967

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 43 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - excitement Behavioral - changes in motor activity (specific assay)

REFERENCE :: BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 106,467,1967

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 175 mg/kg

TOXIC EFFECTS :: Behavioral - hallucinations, distorted perceptions Behavioral - muscle contraction or spasticity Gastrointestinal - nausea or vomiting

REFERENCE :: BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 106,467,1967

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >50 mg/kg

TOXIC EFFECTS :: Behavioral - hallucinations, distorted perceptions Behavioral - muscle contraction or spasticity Gastrointestinal - nausea or vomiting

REFERENCE :: BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 106,467,1967

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 1 gm/kg

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

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,230,1982

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 19 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - excitement Behavioral - changes in motor activity (specific assay)

REFERENCE :: BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 106,467,1967

Safety Information

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
UY0704600

[ HS Code ]:
2933990090

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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