Acetazolamide

Acetazolamide sodium is the sodium salt of Acetazolamide. Acetazolamide is a carbonic anhydrase (CA) IX inhibitor with an IC50 of 30 nM for hCA IX. Acetazolamide has diuretic, antihypertensive and anti-gonococcal activities[1][4][5][6].

Research Areas >> Infection

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Metabolic Enzyme/Protease >> Carbonic Anhydrase

Research Areas >> Metabolic Disease

Signaling Pathways >> Anti-infection >> Bacterial

Acetazolamide also inhibits hCA II with an IC50 of 130 nM[1]. Acetazolamide (Ace) is a small heteroaromatic sulfonamide that binds to various carbonic anhydrases with high affinity, acting as a carbonic anhydrase (CA) inhibitor[2]. Compared with the control group, the high Acetazolamide concentration (AceH, 50 nM), Cisplatin (Cis; 1 µg/mL) and Cis combined with the low Acetazolamide concentration (AceL, 10 nM) treatments significantly reduces viability of Hep-2 cells[2]. Treatment with the Acetazolamide/Cis combination significantly increases the expression levels of P53, as both AceL+Cis and AceH+Cis treatments result in significantly increased P53 protein expression levels compared with the control group. The Ace/Cis combination treatment significantly reduces the bcl-2/bax expression ratio, and increases the expression of caspase-3 protein, compared with the control group. AceL, AceH, Cis and AceL+Cis treatments significantly reduce the bcl-2/bax ratio compared with the control group[2]. Combined Ace and Cis treatment effectively promotes apoptosis in Hep-2 cells[2]. Combined treatment with Ace/Cis markedly decreases the expression of AQP1 mRNA in Hep-2 cells. Both AceH and AceL+Cis treatments decrease the expression of aquaporin-1 (AQP1) mRNA in Hep-2 cells compared with the control group[2].

Acetazolamide (40 mg/kg) significantly potentiates the inhibitory effect of MS-275 on tumorigenesis in neuroblastoma (NB) SH-SY5Y xenografts[3]. Acetazolamide (40 mg/kg) and/or MS-275 treatment reduce expression of HIF1-α and CAIX in NB SH-SY5Y xenograft[3]. Acetazolamide (40 mg/kg), MS-275 and Acetazolamide+MS-275 reduce expression of mitotic and proliferative markers in NB SH-SY5Y xenografts[3].Acetazolamide (50 mg/kg; PO, for 3 days) significantly reduces the gonococcal load in the vagina of infected mice by 90%[6].

[1]. Bayat Mokhtari R, et al. Acetazolamide potentiates the anti-tumor potential of HDACi, MS-275, in neuroblastoma. BMC Cancer. 2017 Feb 24;17(1):156.

[2]. Hou Z, et al. Dual-tail approach to discovery of novel carbonic anhydrase IX inhibitors by simultaneously matching the hydrophobic and hydrophilic halves of the active site. Eur J Med Chem. 2017 May 26;132:1-10.

[3]. Gao H, et al. Combined treatment with acetazolamide and cisplatin enhances chemosensitivity in laryngeal carcinoma Hep-2 cells. Oncol Lett. 2018 Jun;15(6):9299-9306.

[4]. Kassamali R, et al. Acetazolamide: a forgotten diuretic agent. Cardiol Rev. 2011 Nov-Dec;19(6):276-8.

[5]. Jabeen E, et al. Interaction of antihypertensive acetazolamide with nonsteroidal anti-inflammatory drugs. J Photochem Photobiol B. 2013 Aug 5;125:155-63.

[6]. Abutaleb NS, et al. In vivo efficacy of acetazolamide in a mouse model of Neisseria gonorrhoeae infection. Microb Pathog. 2022 Mar;164:105454.

MOLECULAR FORMULA :

C4-H5-N4-O3-S2.Na

MOLECULAR WEIGHT :

244.24

WISWESSER LINE NOTATION :

T5NN DSJ CSZW EMV1 &-NA-

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>1 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JHHBAI Bulletin of the Johns Hopkins Hospital. (Baltimore, MD) V.1-119, 1889-1966. For publisher information, see JHMJAX. Volume(issue)/page/year: 95,199,1954

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JHHBAI Bulletin of the Johns Hopkins Hospital. (Baltimore, MD) V.1-119, 1889-1966. For publisher information, see JHMJAX. Volume(issue)/page/year: 95,199,1954

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

3 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JHHBAI Bulletin of the Johns Hopkins Hospital. (Baltimore, MD) V.1-119, 1889-1966. For publisher information, see JHMJAX. Volume(issue)/page/year: 95,199,1954

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

>2 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JHHBAI Bulletin of the Johns Hopkins Hospital. (Baltimore, MD) V.1-119, 1889-1966. For publisher information, see JHMJAX. Volume(issue)/page/year: 95,199,1954

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

1500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JHHBAI Bulletin of the Johns Hopkins Hospital. (Baltimore, MD) V.1-119, 1889-1966. For publisher information, see JHMJAX. Volume(issue)/page/year: 95,199,1954 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

1 gm/kg/10D-I

TOXIC EFFECTS :

Nutritional and Gross Metabolic - changes in sodium Nutritional and Gross Metabolic - changes in potassium

REFERENCE :

JHHBAI Bulletin of the Johns Hopkins Hospital. (Baltimore, MD) V.1-119, 1889-1966. For publisher information, see JHMJAX. Volume(issue)/page/year: 95,199,1954 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

1 gm/kg

SEX/DURATION :

female 10 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 - fetal death Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 1,51,1968

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1 gm/kg

SEX/DURATION :

female 10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 1,51,1968

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

850 mg/kg

SEX/DURATION :

female 10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 28,355,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1 gm/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 10,221,1974

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

200 mg/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :

TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 27,51,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1 gm/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 28,45,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

3 gm/kg

SEX/DURATION :

female 9-11 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 28,45,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

200 mg/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 28,45,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1500 mg/kg

SEX/DURATION :

female 13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material)

REFERENCE :

TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 15,199,1977

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1500 mg/kg

SEX/DURATION :

female 13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 15,199,1977

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

300 mg/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 4,95,1971

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

600 mg/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System

REFERENCE :

TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 4,95,1971

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravaginal

DOSE :

110 mg/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 7,209,1973 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5616 No. of Facilities: 17 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 223 (estimated) No. of Female Employees: 137 (estimated)