Tolbutamide

Tolbutamide is a first generation potassium channel blocker, sulfonylurea oral hypoglycemic drug.Target: Potassium ChannelTolbutamide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). Tolbutamide act by stimulating β cells of the pancreas to release insulin. Sulfonylureas increase both basal insulin secretion and meal-stimulated insulin release. Tolbutamide belongs to a class of medications called sulfonylureas. Tolbutamide inhibits both the basal and the cyclic AMP-stimulated protein kinase activities and the IC50 of Tolbutamide is 4 mM. Similar Tolbutamide concentrations are required for half maximal inhibition of in vitro lipolysis induced by hormones (norepinephrine and ACTH) or by dibutyryl cyclic AMP plus theophylline. Tolbutamide also inhibits both soluble and membrane-bound protein kinase from canine heart. The Tolbutamide inhibition of adipose tissue cyclic AMP-dependent protein kinase is one possible explanation for the antilipolytic effects of this drug [1]. Tolbutamide inhibits C6-glioma cell proliferation by increasing Cx43, which correlates with a reduction in pRb phosphorylation due to the up-regulation of the Cdk inhibitors p21 and p27 [2].

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Research Areas >> Metabolic Disease

[1]. Wray, H.L. and A.W. Harris, Adenosine 3', 5'-monophosphate-dependent protein kinase in adipose tissue: inhibition by tolbutamide. Biochem Biophys Res Commun, 1973. 53(1): p. 291-4.

[2]. Sanchez-Alvarez, R., et al., Tolbutamide reduces glioma cell proliferation by increasing connexin43, which promotes the up-regulation of p21 and p27 and subsequent changes in retinoblastoma phosphorylation. Glia, 2006. 54(2): p. 125-34.

Nigericin sodium salt | Senicapoc | E-4031 | 4-AMINOPYRIDINE | Ginsenoside Rg3 | TRAM-34 | Dofetilide | PAP-1 | Minoxidil | Flufenamic Acid | Flupirtine maleate | NS-1619 | Endoxifen (Z-isomer hydrochloride) | NS309 | Quinine

DATA ITEMS CITED :

40

MOLECULAR FORMULA :

C12-H18-N2-O3-S

MOLECULAR WEIGHT :

270.38

WISWESSER LINE NOTATION :

4MVMSWR D1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

1 gm/kg

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting Endocrine - hypoglycemia

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2490 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 - 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 :

700 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 :

490 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 :

650 mg/kg

TOXIC EFFECTS :

Behavioral - ataxia Endocrine - hypoglycemia Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

980 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 :

770 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 :

Unreported

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

700 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 :

Mammal - species unspecified

DOSE/DURATION :

750 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

2 mg/kg

SEX/DURATION :

female 1-13 week(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Effects on Newborn - other neonatal measures or effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

2600 mg/kg

SEX/DURATION :

female 1-37 week(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - urogenital system Reproductive - Effects on Newborn - other neonatal measures or effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

1800 mg/kg

SEX/DURATION :

female 26-39 week(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - stillbirth

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3 gm/kg

SEX/DURATION :

female 10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

12 gm/kg

SEX/DURATION :

female 1-12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - abortion Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

8400 mg/kg

SEX/DURATION :

male 3 day(s) pre-mating female 3 day(s) pre-mating - 22 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

70 mg/kg

SEX/DURATION :

female 7-13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Effects on Newborn - live birth index (measured after birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

1650 mg/kg

SEX/DURATION :

female 1-22 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - biochemical and metabolic

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

5400 mg/kg

SEX/DURATION :

female 9-14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - eye/ear

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1700 mg/kg

SEX/DURATION :

female 1-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1250 mg/kg

SEX/DURATION :

female 2 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

400 mg/kg

SEX/DURATION :

female 13 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 :

1800 mg/kg

SEX/DURATION :

female 8-16 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 - cardiovascular (circulatory) system Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

Sister chromatid exchange

TYPE OF TEST :

Sister chromatid exchange

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Sister chromatid exchange

MUTATION DATA

TEST SYSTEM :

Rodent - hamster

DOSE/DURATION :

28600 ug/kg

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 77,349,1980 *** REVIEWS *** TOXICOLOGY REVIEW KDYIA5 Kidney International. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus Secaucus, NJ 07094) V.1- 1972- Volume(issue)/page/year: 10,82,1976 TOXICOLOGY REVIEW INTEAG Internist. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1960- Volume(issue)/page/year: 15,7,1974 TOXICOLOGY REVIEW ARVPAX Annual Review of Pharmacology. (Palo Alto, CA) V.1-15, 1961-75. For publisher information, see ARPTDI. Volume(issue)/page/year: 5,447,1965 TOXICOLOGY REVIEW ADVPA3 Advances in Pharmacology. (New York, NY) V.1-6, 1962-68. For publisher information, see AVPCAQ. Volume(issue)/page/year: 4,263,1966 TOXICOLOGY REVIEW LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 2,1424,1960 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4772 No. of Facilities: 66 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 857 (estimated) No. of Female Employees: 600 (estimated)