Triamterene

Triamterene blocks epithelial Na+ channel (ENaC) in a voltage-dependent manner, which used as a mild diuretic.Target: Sodium ChannelTriamterene blocked rENaC in a voltage-dependent manner, and was 100-fold less potent than amiloride at pH 7.5. At -90 mV and -40 mV, the IC50 values were 5 microM and 10 microM, respectively. The blockage by triamterene, which is a weak base with a pKa of 6.2, was dependent on the extracellular pH. The IC50 was 1 microM at pH 6.5 and only 17 microM at pH 8.5 [1]. Triamterene (TA) is partly eliminated by a first-pass-effect. The main metabolite of TA is OH-TA-ester, which is pharmacologically active [2].

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

Research Areas >> Metabolic Disease

[1]. Busch, A.E., et al., Blockade of epithelial Na+ channels by triamterenes - underlying mechanisms and molecular basis. Pflugers Arch, 1996. 432(5): p. 760-6.

[2]. Gilfrich, H.J., et al., Pharmacokinetics of triamterene after i.v. administration to man: determination of bioavailability. Eur J Clin Pharmacol, 1983. 25(2): p. 237-41.

EIPA | Riluzole | Ginsenoside Rg3 | Cariporide | Eleclazine hydrochloride | GS967 | Tenapanor | Ranolazine dihydrochloride | PF 05089771 | flecainide acetate | A-803467 | CNV1014802 (hydrochloride) | Zonisamide | Cinchocaine | ICA 121431

DATA ITEMS CITED :

21

MOLECULAR FORMULA :

C12-H11-N7

MOLECULAR WEIGHT :

253.30

WISWESSER LINE NOTATION :

T66 BN DN GN JNJ CZ EZ HR& IZ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

42 mg/kg/3W-I

TOXIC EFFECTS :

Liver - hepatitis (hepatocellular necrosis), zonal Nutritional and Gross Metabolic - body temperature increase

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

400 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 :

200 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 :

285 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 :

249 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 :

620 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 :

25077 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

25 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

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

157 mg/kg/3W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2700 mg/m3/15D-C

TOXIC EFFECTS :

Endocrine - other changes 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 :

6370 mg/m3/13W-C

TOXIC EFFECTS :

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

DOSE/DURATION :

8190 mg/kg/13W-C

TOXIC EFFECTS :

Endocrine - other changes Blood - changes in leukocyte (WBC) count 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 :

21840 mg/kg/2Y-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

34944 mg/kg/2Y-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Liver - tumors

MUTATION DATA

TYPE OF TEST :

Sister chromatid exchange

TEST SYSTEM :

Rodent - hamster Lung

DOSE/DURATION :

12600 ug/L

REFERENCE :

SNSHBT Senshokutai. Chromosome. (Sensyokutai Gakkai, Kaokusai Kirisutokyo Daigaku, Mitaka, Tokyo-to, Japan) No.1- 1946- Adopted new numbering in 1976. Volume(issue)/page/year: (20),574,1980 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5679 No. of Facilities: 60 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 587 (estimated) No. of Female Employees: 310 (estimated)