tolmetin sodium

Tolmetin sodium is an orally active and potent COX inhibitor with IC50s of 0.35 µM and 0.82 µM human COX-1 and COX-2, respectively. Tolmetin sodium is a non-steroidal anti-inflammatory drug (NSAID)[1][2].

Research Areas >> Cancer

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Immunology/Inflammation >> COX

Human COX-1:0.35 μM (IC50)

Human COX-2:0.82 μM (IC50)

Tolmetin sodium (0.25 mM) does not attenuate lipid peroxidation in rat brain homogenate. Tolmetin (0.25, 0.5, 0.75, 1 mM) shows radical scavenging properties but without superoxide anion generation in rat brain homogenat[3]. Tolmetin sodium (0.001-100 μM) shows anticancer activity againts HT-29 colon cancer cell line in a dose-dependent manner[4]. Tolmetin sodium (0-100 μM) shows no effect on osteoblast growth[5].

Tolmetin sodium (30,100 mg/kg; gavage; single dose or twice daily for 3 and 14 days) shows maximal ulcerogenic effect 4 h after the single dose, while potently decreases after 3 and 14 days of repeated administration in male Wistar rats weighing 180-200 g. Tolmetin causes gastric lesions in 100 mg/kg[2]. Tolmetin sodium (5 mg/kg twice a day for 5 days) pre-treatment considerably attenuates quinolinic acid (QA)-induced neurotoxicity[3].

[1]. T D Warner, et al. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7563-8.

[2]. Etcheverry SB, et al. Three new vanadyl(IV) complexes with non-steroidal anti-inflammatory drugs (Ibuprofen, Naproxen and Tolmetin). Bioactivity on osteoblast-like cells in culture. J Inorg Biochem. 2002 Jan 1;88(1):94-100.

[3]. DADAŞ, Yakup, et al. Synthesis and anticancer activity of some novel tolmetin thiosemicarbazides. Marmara Pharmaceutical Journal 19(3) • April 2015

MOLECULAR FORMULA :

C14-H12-N-O3.Na

MOLECULAR WEIGHT :

265.26

WISWESSER LINE NOTATION :

T5MJ BVR D1& E1VO &-NA-

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

2520 mg/kg/8W-I

TOXIC EFFECTS :

Blood - thrombocytopenia

REFERENCE :

ARHEAW Arthritis and Rheumatism. (Arthritis Foundation, 1314 Spring St., NW, Atlanta, GA 30309) V.1- 1958- Volume(issue)/page/year: 25,1144,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

538 mg/kg/61D-I

TOXIC EFFECTS :

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

REFERENCE :

JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 243,1263,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

8 mg/kg

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions Vascular - BP lowering not characterized in autonomic section Vascular - shock

REFERENCE :

JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 240,246,1978

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

8 mg/kg

TOXIC EFFECTS :

Spinal Cord - meningeal changes Sense Organs and Special Senses (Eye) - conjunctive irritation Liver - liver function tests impaired

REFERENCE :

JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 245,67,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

914 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 1,233,1977

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

770 mg/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: 6,532,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1050 mg/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: 6,532,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>724 mg/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: 6,532,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

899 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 1,233,1977

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

690 mg/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: 6,532,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

670 mg/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: 6,532,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>622 mg/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: 6,532,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

>800 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 1,233,1977

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

1584 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 1,233,1977 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

100 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: 38,238,1982 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5369 No. of Facilities: 53 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 2069 (estimated) No. of Female Employees: 1109 (estimated)