Meclizine dihydrochloride

Meclizine is a histamine H1 receptor antagonist used to treat nausea and motion sicknessTarget: Histamine H1 ReceptorMeclizine is a histamine H1 receptor antagonist used to treat nausea and motion sickness, possesses anticholinergic, central nervous system depressant, and local anesthetic effects [1]. Meclizine is an agonist ligand for mouse CAR (constitutive androstane receptor), and an inverse agonist for human CAR. Meclizine increases mCAR transactivation in a dose-dependent manner, stimulates binding of steroid receptor coactivator 1 to the murine receptor in vitro. In contrast, meclizine suppresses hCAR transactivation and inhibits the phenobarbital-induced expression of the CAR target genes, cytochrome p450 monooxygenase (CYP)2B10, CYP3A11, and CYP1A2, in primary hepatocytes derived from mice expressing hCAR, but not mCAR [2].

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

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Neurological Disease

[1]. King, C.T., S.A. Weaver, and S.A. Narrod, Antihistamines and Teratogenicity in the Rat. J Pharmacol Exp Ther, 1965. 147: p. 391-8.

[2]. Huang, W., et al., Meclizine is an agonist ligand for mouse constitutive androstane receptor (CAR) and an inverse agonist for human CAR. Mol Endocrinol, 2004. 18(10): p. 2402-8.

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

MOLECULAR FORMULA :

C25-H27-Cl-N2.2Cl-H

MOLECULAR WEIGHT :

463.91

WISWESSER LINE NOTATION :

T6N DNTJ AYR&R DG& D1R C1 &GH 2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1600 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

29ZVAB "Handbook of Analytical Toxicology," Sunshine, I., ed., Cleveland, OH, Chemical Rubber Co., 1969 Volume(issue)/page/year: -,67,1969

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

625 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - excitement Lungs, Thorax, or Respiration - respiratory obstruction

REFERENCE :

JAPMA8 Journal of the American Pharmaceutical Association, Scientific Edition. (Washington, DC) V.29-49, 1940-60. For publisher information, see JPMSAE. Volume(issue)/page/year: 43,653,1954 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

800 mg/kg

SEX/DURATION :

female 8-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - homeostasis Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

REFERENCE :

MPHEAE Medicina et Pharmacologia Experimentalis. (Basel, Switzerland) V.12-17, 1965-67. For publisher information, see PHMGBN. Volume(issue)/page/year: 15,375,1966

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

800 mg/kg

SEX/DURATION :

female 8-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

MPHEAE Medicina et Pharmacologia Experimentalis. (Basel, Switzerland) V.12-17, 1965-67. For publisher information, see PHMGBN. Volume(issue)/page/year: 15,375,1966

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1 gm/kg

SEX/DURATION :

female 8-15 day(s) after conception

TOXIC EFFECTS :

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

REFERENCE :

MPHEAE Medicina et Pharmacologia Experimentalis. (Basel, Switzerland) V.12-17, 1965-67. For publisher information, see PHMGBN. Volume(issue)/page/year: 15,375,1966