Hydroxyzine

Hydroxyzine 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

DATA ITEMS CITED :

11

MOLECULAR FORMULA :

C21-H27-Cl-N2-O2

MOLECULAR WEIGHT :

374.95

WISWESSER LINE NOTATION :

T6N DNTJ AYR&R D6& D2O2Q

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 :

840 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CHTPBA Chimica Therapeutica. (Paris, France) V.1-8, 1965-73. For publisher information, see EJMCA5. Volume(issue)/page/year: 3,210,1968

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

160 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CHTPBA Chimica Therapeutica. (Paris, France) V.1-8, 1965-73. For publisher information, see EJMCA5. Volume(issue)/page/year: 3,210,1968

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 :

ANPBAZ Acta Neurologia et Psychiatrica Belgica. (Brussels, Belgium) V.48-69, 1948-69. For publisher information, see ANUBBR. Volume(issue)/page/year: 61,669,1961

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

400 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CHTPBA Chimica Therapeutica. (Paris, France) V.1-8, 1965-73. For publisher information, see EJMCA5. Volume(issue)/page/year: 3,210,1968

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

81300 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DPHFAK Dissertationes Pharmaceuticae et Pharmacologicae. (Warsaw, Poland) V.18-24, 1966-72. For publisher information, see PJPPAA. Volume(issue)/page/year: 23,281,1971

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

137 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: -,237,1972 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

400 mg/kg

SEX/DURATION :

female 13-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - homeostasis

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 17,67,1970

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

40 mg/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

REFERENCE :

FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 12,346,1961

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

350 mg/kg

SEX/DURATION :

female 15-21 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

28QFAD "Laboratory Animals in Drug Testing, Symposium of the 5th International Committee on Laboratory Animals, Hanover, 1972," Speigel, A. ed., Stuttgart, Fed. Rep. Ger., Gustav Fischer Verlag, 1973 Volume(issue)/page/year: -,233,1973

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1500 mg/kg

SEX/DURATION :

female 1-60 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - stillbirth

REFERENCE :

28QFAD "Laboratory Animals in Drug Testing, Symposium of the 5th International Committee on Laboratory Animals, Hanover, 1972," Speigel, A. ed., Stuttgart, Fed. Rep. Ger., Gustav Fischer Verlag, 1973 Volume(issue)/page/year: -,233,1973 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6151 No. of Facilities: 52 (estimated) No. of Industries: 1 No. of Occupations: 3 No. of Employees: 1362 (estimated) No. of Female Employees: 719 (estimated)