Cimetidine

Cimetidine is a histamine-2 (H2) receptor antagonist.IC50 Value: Target: Histamine-2 Receptorin vitro: Cimetidine, a partial agonist for H2R, has a pharmacological profile different from ranitidine and famotidine, possibly contributing to its antitumor activity on gastrointestinal cancers [1]. Cimetidine had no effect on the uptake and cytotoxicity of cisplatin in ovarian cancer cells with high OCT2 mRNA levels (IGROV-1 cells) [2]. Cimetidine showed no effect on proliferation, survival, migration and invasion of 3LL cells. Cimetidine reversed MDSC-mediated T-cell suppression, and improved IFN-γ production. [3]. Cimetidine-mediated down-regulation of NCAM involved suppression of the nuclear translocation of NF-kappaB, a transcriptional activator of NCAM gene expression [4].in vivo: the antitumor efficacy of cisplatin in mice bearing luciferase-tagged IGROV-1 xenografts was unaffected by cimetidine (P = 0.39). Data obtained in 18 patients receiving cisplatin (100 mg/m(2)) in a randomized crossover fashion with or without cimetidine (800 mg × 2) revealed that cimetidine did not alter exposure to unbound cisplatin [2]. cimetidine reduced CD11b(+)Gr-1(+) myeloid derived-suppressive cell (MDSC) accumulation in spleen, blood and tumor tissue of tumor-bearing mice [3]. Cimetidine exerts a beneficial effect on periodontal disease in rats, decreasing the RANKL/OPG ratio in gingival connective tissue and reducing alveolar bone resorption [5].

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

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Cancer

[1]. Takahashi, H.K., et al., Cimetidine induces interleukin-18 production through H2-agonist activity in monocytes. Mol Pharmacol, 2006. 70(2): p. 450-3.

[2]. Sprowl, J.A., et al., Conjunctive therapy of cisplatin with the OCT2 inhibitor cimetidine: influence on antitumor efficacy and systemic clearance. Clin Pharmacol Ther, 2013. 94(5): p. 585-92.

[3]. Zheng, Y., et al., Cimetidine suppresses lung tumor growth in mice through proapoptosis of myeloid-derived suppressor cells. Mol Immunol, 2013. 54(1): p. 74-83.

[4]. Fukuda, M., K. Kusama, and H. Sakashita, Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression. BMC Cancer, 2008. 8: p. 376.

[5]. Longhini, R., et al., Cimetidine Reduces the Alveolar Bone Loss in Induced Periodontitis in Rat Molars. J Periodontol, 2013.

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

MOLECULAR FORMULA :

C10-H16-N6-S

MOLECULAR WEIGHT :

252.38

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

51 mg/kg/3D-I

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

30 mg/kg/2D-I

TOXIC EFFECTS :

Behavioral - ataxia Behavioral - rigidity (including catalepsy) Behavioral - muscle contraction or spasticity

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

2857 ug/kg

TOXIC EFFECTS :

Cardiac - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

57 mg/kg/5D-I

TOXIC EFFECTS :

Liver - jaundice, cholestatic

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

80 mg/kg/8D

TOXIC EFFECTS :

Vascular - BP lowering not characterized in autonomic section Blood - leukopenia Nutritional and Gross Metabolic - body temperature increase

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

270 mg/kg/3W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - interstitial nephritis

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

4286 ug/kg/30M-C

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - dyspnea Skin and Appendages - sweating

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Cardiac - pulse rate increase, without fall in BP

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

1008 mg/kg/6W-I

TOXIC EFFECTS :

Vascular - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

4 mg/kg/2M-C

TOXIC EFFECTS :

Cardiac - pulse rate increase, without fall in BP

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

600 mg/kg/6W

TOXIC EFFECTS :

Skin and Appendages - hair

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

5 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

328 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

860 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

106 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2550 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

306 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

437 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

150 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

2600 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

206 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - effect, not otherwise specified Gastrointestinal - other changes

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

>8640 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

1063 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

164 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

4 gm/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

880 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

60 gm/kg/30D-C

TOXIC EFFECTS :

Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

364 gm/kg/26W-C

TOXIC EFFECTS :

Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

123 gm/kg/13W-I

TOXIC EFFECTS :

Liver - changes in liver weight Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - changes in prostate weight

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1400 mg/kg/14D-I

TOXIC EFFECTS :

Immunological Including Allergic - increase in cellular immune response Immunological Including Allergic - increase in humoral immune response Immunological Including Allergic - increased immune response

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

7392 mg/kg/11D-I

TOXIC EFFECTS :

Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

15600 mg/kg/2Y-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Reproductive - Tumorigenic effects - testicular tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

13300 mg/kg male 2 week(s) pre-mating female 2 week(s) pre-mating - 3 week(s) post-birth

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Reproductive - Tumorigenic effects - transplacental tumorigenesis Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

39312 mg/kg/2Y-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Reproductive - Tumorigenic effects - testicular tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

720 mg/kg

SEX/DURATION :

female 33-37 week(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - hepatobiliary system Reproductive - Effects on Newborn - Apgar score (human only)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

700 mg/kg

SEX/DURATION :

male 7 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

4384 mg/kg

SEX/DURATION :

female 12-22 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - urogenital system Reproductive - Effects on Newborn - delayed effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

4950 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1650 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

14850 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - live birth index (measured after birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

2100 mg/kg

SEX/DURATION :

lactating female 42 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - biochemical and metabolic

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

1820 mg/kg

SEX/DURATION :

male 26 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

MUTATION DATA

TYPE OF TEST :

Unscheduled DNA synthesis

TEST SYSTEM :

Rodent - rat Liver

DOSE/DURATION :

1 mmol/L

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 120,133,1983 *** REVIEWS *** IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,235,1990 IARC Cancer Review:Animal Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,235,1990 IARC Cancer Review:Group 3 IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,235,1990 TOXICOLOGY REVIEW SUMEA4 Suvremenna Meditsina. Modern Medicine. (Hemus, Blvd. Russki 6, Sofia, Bulgaria) V.1- 1951- Volume(issue)/page/year: 32,472,1981 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3652 No. of Facilities: 248 (estimated) No. of Industries: 1 No. of Occupations: 5 No. of Employees: 11103 (estimated) No. of Female Employees: 9115 (estimated)