Furosemide

Furosemide (Lasix) is a loop diuretic inhibitor of Na+/2Cl-/K+ (NKCC) cotransporter of which used in the treatment of congestive heart failure and edema.Target: NKCC Furosemide (INN/BAN) or frusemide is a loop diuretic used in the treatment of congestive heart failure and edema. It is most commonly marketed by Sanofi under the brand name Lasix, and also under the brand names Fusid and Frumex. It has also been used to prevent Thoroughbred and Standardbred race horses from bleeding through the nose during races.Along with some other diuretics, furosemide is also included on the World Anti-Doping Agency's banned drug list due to its alleged use as a masking agent for other drugs.Furosemide, like other loop diuretics, acts by inhibiting NKCC2, the luminal Na-K-2Cl symporter in the thick ascending limb of the loop of Henle. The action on the distal tubules is independent of any inhibitory effect on carbonic anhydrase or aldosterone; it also abolishes the corticomedullary osmotic gradient and blocks negative, as well as positive, free water clearance.Because of the large NaCl absorptive capacity of the loop of Henle, diuresis is not limited by development of acidosis, as it is with the carbonic anhydrase inhibitors. Additionally, furosemide is a noncompetitive subtype-specific blocker of GABA-A receptors. Furosemide has been reported to reversibly antagonize GABA-evoked currents of α6β2γ2 receptors at uM concentrations, but not α1β2γ2 receptors. During development, the α6β2γ2 receptor increases in expression in cerebellar granule neurons, corresponding to increased sensitivity to furosemide

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

Research Areas >> Metabolic Disease

[1]. Rais-Bahrami K, et al. Use of furosemide and hearing loss in neonatal intensive care survivors. Am J Perinatol. 2004 Aug;21(6):329-32.

[2]. Tia S, et al. Developmental changes of inhibitory synaptic currents in cerebellar granule neurons: role of GABA (A) receptor alpha 6 subunit. J Neurosci. 1996 Jun 1;16(11):3630-40.

[3]. Korpi ER, et al. Selective antagonist for the cerebellar granule cell-specific gamma-aminobutyric acid type A receptor. Mol Pharmacol.1995 Feb;47(2):283-9.

Furosemide (sodium)

DATA ITEMS CITED :

49

MOLECULAR FORMULA :

C12-H11-Cl-N2-O5-S

MOLECULAR WEIGHT :

330.76

WISWESSER LINE NOTATION :

T5OJ B1MR CG FVQ DSZW

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

120 mg/kg/21W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - interstitial nephritis

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

29 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Ear) - change in acuity Sense Organs and Special Senses (Ear) - tinnitus Kidney, Ureter, Bladder - urine volume decreased

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

6250 ug/kg

TOXIC EFFECTS :

Behavioral - muscle weakness Nutritional and Gross Metabolic - changes in calcium Nutritional and Gross Metabolic - changes in metals, not otherwise specified

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

1300 ug/kg

TOXIC EFFECTS :

Cardiac - other changes Vascular - regional or general arteriolar constriction

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - infant

DOSE/DURATION :

1 mg/kg/4H-I

TOXIC EFFECTS :

Nutritional and Gross Metabolic - metabolic alkalosis

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

2500 ug/kg/2M-C

TOXIC EFFECTS :

Cardiac - pulse rate

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

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 :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

800 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 :

800 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 :

2 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 :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

308 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 :

900 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 :

2 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 :

Intravenous

SPECIES OBSERVED :

Mammal - dog

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 :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

800 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 :

400 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 :

1400 mg/kg/5W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - urine volume increased Liver - changes in liver weight

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

32200 mg/kg/14D-C

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

27300 mg/kg/13W-I

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

15288 mg/kg/26W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - urine volume increased Kidney, Ureter, Bladder - changes in bladder weight Nutritional and Gross Metabolic - changes in sodium

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

77280 mg/kg/14D-C

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

54600 mg/kg/13W-I

TOXIC EFFECTS :

Liver - changes in liver weight

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

21112 mg/kg/2Y-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Brain and Coverings - tumors Kidney, Ureter, Bladder - Kidney tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

15652 mg/kg/2Y-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Skin and Appendages - tumors Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

122 gm/kg/2Y-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Skin and Appendages - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

150 mg/kg

SEX/DURATION :

female 12-14 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 :

300 mg/kg

SEX/DURATION :

female 16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

122 mg/kg

SEX/DURATION :

male 6 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

150 mg/kg

SEX/DURATION :

female 16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

1800 mg/kg

SEX/DURATION :

female 6-17 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 :

12500 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

5 gm/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

1560 ug/kg

SEX/DURATION :

male 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :

Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :

Sister chromatid exchange

TEST SYSTEM :

Rodent - hamster Ovary

DOSE/DURATION :

500 mg/L

REFERENCE :

NTPTR* National Toxicology Program Technical Report Series. (Research Triangle Park, NC 27709) No.206- Volume(issue)/page/year: NTP-TR-356,1989 *** 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: 50,277,1990 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: 50,277,1990 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: 50,277,1990 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 84036 No. of Facilities: 25 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 275 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 84036 No. of Facilities: 202 (estimated) No. of Industries: 1 No. of Occupations: 7 No. of Employees: 14103 (estimated) No. of Female Employees: 11997 (estimated)