Hydroxyzine dihydrochloride

Hydroxyzine Dihydrochloride is a histamine H1-receptor antagonist.Target: Histamine H1-ReceptorHydroxyzine inhibits carbachol (10 μM)-induced serotonin release by 34% at 10 μM, by 25% 1 μM and by 17% 0.1 μM in pretreated bladder slices for 60 min [1]. Hydroxyzine (0.1 mM) treatment inhibits the progression and severity of EAE by 50% and the extent of mast cell degranulation by 70% in Lewis rats with allergic encephalomyelitis (EAE) [2]. Hydroxyzine (500 M) significantly increases transport of etoposide to the serosal site in the jejunal everted sacs. Hydroxyzine significantly reduces the efflux and approximately 2.4 g/mL of etoposide in the jejunum and ileum. Hydroxyzine (0.2 μg/mL) significantly enhances the efflux of RH123 to the lumen [3].Hydroxyzine (500 μM) significantly decreases the steady-state etoposide concentration 2-fold, where the steady-state concentration reached about 0.055 μM/mL in Sprague-Dawley rats [3]. Hydroxyzine (12.5 mg/kg, 25 mg/kg and 50 mg/kg i.p.) shows little direct analgesic activity but markedly potentiates only the effect of morphine on the vocalization after-discharge which represents the affective component of pain in rats. Hydroxyzine (50 mg/kg i.p.) potentiates morphine on the tail-flick test, while Hydroxyzine (12.5 mg/kg i.p.) decreases morphine antinociception in rats [4].

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

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Inflammation/Immunology

[1]. Minogiannis, P., et al., Hydroxyzine inhibits neurogenic bladder mast cell activation. Int J Immunopharmacol, 1998. 20(10): p. 553-63.

[2]. Dimitriadou, V., X. Pang, and T.C. Theoharides, Hydroxyzine inhibits experimental allergic encephalomyelitis (EAE) and associated brain mast cell activation. Int J Immunopharmacol, 2000. 22(9): p. 673-84.

[3]. Kan, W.M., et al., Effect of hydroxyzine on the transport of etoposide in rat small intestine. Anticancer Drugs, 2001. 12(3): p. 267-73.

[4]. Morichi, R. and G. Pepeu, A study of the influence of hydroxyzine and diazepam on morphine antinociceptoion in the rat. Pain, 1979. 7(2): p. 173-80.

Loratadine | Histamine | Pitolisant hydrochloride | Cimetidine | Osthole | Clemastine fumarate | Ebrotidine | JNJ-7777120 | Famotidine | Cetirizine Dihydrochloride | Desloratadine | Ketotifen fumarate | Lodoxamide | Meclizine dihydrochloride | Chlorpheniramine maleate

MOLECULAR FORMULA :

C21-H27-Cl-N2-O2.2Cl-H

MOLECULAR WEIGHT :

447.87

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

500 ug/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex)

REFERENCE :

HUPSEC Human Psychopharmacology. (John Wiley & Sons Ltd., Baffins Lane, Chichester, W.Sussex PO19 1UD, United Kingdom) V.1- 1986- Volume(issue)/page/year: 7,25,1992

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

357 ug/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex)

REFERENCE :

HUPSEC Human Psychopharmacology. (John Wiley & Sons Ltd., Baffins Lane, Chichester, W.Sussex PO19 1UD, United Kingdom) V.1- 1986- Volume(issue)/page/year: 7,25,1992

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

750 ug/kg

TOXIC EFFECTS :

Skin and Appendages - dermatitis, other (after systemic exposure)

REFERENCE :

APHRER Annals of Pharmacotherpy. (Harvey Whitney Books Co., POB 42696, Cincinnati, OH 45242) V. 26- 1992- Volume(issue)/page/year: 31,327,1997

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

950 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 18,185,1971

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

126 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 18,185,1971

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

45 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 109,127,1957

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

122 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 24,100,1973

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

48900 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 24,100,1973 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 84615 No. of Facilities: 1397 (estimated) No. of Industries: 2 No. of Occupations: 2 No. of Employees: 2782 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 84615 No. of Facilities: 42 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 1296 (estimated) No. of Female Employees: 1246 (estimated)