Infected macrophages treated with ethoxzolamide (ETZ) showed >90% quantification of reporter GFP fluorescence. Moreover, treatment with ethoxzolamide (ETZ) dramatically slowed the increase of M's intracellular expression. TB in a 9-day transient macrophage test [2].

It was discovered that the body converted fat-soluble ethoxazolamide into dissolved lysates while keeping high enzyme activity. The IOP decreased by 4.2 mmHg, the concentration in the anterior uvea was 2.5 pmol/kg, and the fractional inhibition of enzyme (i) was 0.9995 at the lowest dose that produced the greatest effect (4 mg/kg iv over 45 minutes). The drug's short half-life in the rose membrane causes a slow release of the drug in the anterior uvea and other tissues, which results in a rapid decrease in effect. In mouse lungs, ethoxzolamide (ETZ) strongly captures GFP reporter fluorescence; in comparison to the ratio of mock-treated controls, the GFP signal was inhibited three times. mice's heart tissue after ETZ treatment in comparison to mock-treated controls1]. There is a notable decrease in the rate [2].

Absorption, Distribution and Excretion
Rapidly absorbed with 65% bioavailability
ABSORBED FROM GI TRACT...DISTRIBUTED IN PLASMA, MUSCLES, BRAIN, KIDNEYS, LIVER, LUNGS, ERYTHROCYTES, AQUEOUS HUMOR, & CSF. APPROX 40%...EXCRETED UNCHANGED BY KIDNEYS /HUMAN, ORAL/

---

Biological Half-Life
2.5-5.5 hours

Protein Binding
~89%

---

Interactions
PATIENTS RECEIVING DIGITALIS GLYCOSIDES, HYPOKALEMIA MAY PREDISPOSE PATIENT TO DIGITALIS TOXICITY & POSSIBLY FATAL CARDIAC ARRHYTHMIAS MAY RESULT... DIURETICS, CORTICOSTEROIDS, CORTICOTROPIN & AMPHOTERICIN B /USED CONCOMITANTLY WITH CARBONIC ANHYDRASE INHIBITORS MAY CAUSE SEVERE HYPOKALEMIA/
CARBONIC ANHYDRASE INHIBITORS MAY AUGMENT EFFECTS OF OTHER DIURETICS SUCH AS THIAZIDES.../USEFUL/ IN ENHANCING & RESTORING RESPONSIVENESS TO MERCURIAL DIURETICS...RARELY, /DRUG/ MAY INTERFERE WITH HYPOGLYCEMIC RESPONSE TO INSULIN OR ORAL HYPOGLYCEMIC DRUGS, POSSIBLY BY CAUSING HYPOKALEMIA.
ALKALINIZATION OF URINE PRODUCED BY /DRUG INCREASES/ RATE OF EXCRETION OF WEAK ACIDS, INCLUDING PHENOBARBITAL & SALICYLATES...METHENAMINE, METHENAMINE HIPPURATE, & METHENAMINE MANDELATE...MAY BE INACTIVE IN ALKALINE URINE PRODUCED BY CARBONIC ANHYDRASE INHIBITORS.
CARBONIC ANHYDRASE INHIBITORS INCREASE EXCRETION OF LITHIUM...ALKALINIZATION OF URINE PRODUCED BY /DRUG/ MAY DECREASE RATE OF EXCRETION OF...AMPHETAMINES, PROCAINAMIDE, QUINIDINE...TRICYCLIC ANTIDEPRESSANTS & /THEIR EFFECTS/ MAY BE ENHANCED &/OR PROLONGED.

[1]. Relations among IOP reduction, ocular disposition and pharmacology of the carbonic anhydrase inhibitor ethoxzolamide. Exp Eye Res. 1992 Jul;55(1):73-9.

[2]. The Carbonic Anhydrase Inhibitor Ethoxzolamide Inhibits theMycobacterium tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence. Antimicrob Agents Chemother. 2015 Aug; 59(8): 4436–4445.

[3]. Development and validation of an UPLC-MS/MS method for the quantification of ethoxzolamide in plasma and bioequivalent buffers: Applications to absorption, brain distribution, and pharmacokinetic studies. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Apr 1; 0: 54–59.

Ethoxzolamide is a sulfonamide that is 1,3-benzothiazole-2-sulfonamide which is substituted by an ethoxy group at position 6. A carbonic anhydrase inhibitor, it has been used in the treatment of glaucoma, and as a diuretic. It has a role as an EC 4.2.1.1 (carbonic anhydrase) inhibitor, a diuretic and an antiglaucoma drug. It is a member of benzothiazoles, a sulfonamide and an aromatic ether.
Ethoxzolamide is a sulfonamide used as diuretic and in glaucoma. It inhibits carbonic anhydrase activity in proximal renal tubules to decrease reabsorption of water, sodium, potassium, bicarbonate. Its pharmacological activity thus confers the risk for hypokalemia.
Ethoxzolamide is a sulfonamide and carbonic anhydrase (CA) inhibitor with diuretic and anti-glaucoma activity. In the eye, ethoxzolamide inhibits CA, thereby decreasing the secretion of aqueous humor. This may relieve intraocular pressure. Also, this agent prevents reabsorption of bicarbonate and sodium in the proximal convoluted tubule thereby producing a mild diuresis.
A carbonic anhydrase inhibitor used as diuretic and in glaucoma. It may cause hypokalemia.

---

Drug Indication
For use in the treatment of duodenal ulcers, as a diuretic, and in the treatment of glaucoma, and may also be useful in the treatment of seizures associated with epilepsy.

---

Mechanism of Action
Ethoxzolamide binds to and inhibits carbonic anhydrase I, which plays an essential role in facilitating the transport of CO2 and H+ in the intracellular space, across biological membranes, and in the layers of the extracellular space. Through inhibition of the enzyme, the balance of applicable membrane equilibrium systems are affected.
MAJOR PHARMACOLOGICAL ACTION...IS INHIBITION OF...CARBONIC ANHYDRASE. STUDIES WITH PURIFIED ENZYME HAVE SHOWN THAT INHIBITION IS NONCOMPETITIVE. NONCATALYZED HYDRATION OR DEHYDRATION REACTION CAN TAKE PLACE, OF COURSE, IN ABSENCE OF ENZYME.
CARBONIC ANHYDRASE INHIBITORS...DECR CONCN OF HYDROGEN IONS AVAIL FOR EXCHANGE WITH SODIUM & POTASSIUM & TO COMBINE WITH BICARBONATE TO FORM CARBONIC ACID. /CARBONIC ANHYDRASE INHIBITORS/
...EFFECT /OF CARBONIC ANHYDRASE INHIBITORS/ ON INTRAOCULAR PRESSURE DOES NOT DEPEND UPON DIURESIS. THEY REDUCE AQUEOUS PRODN ... & THUS LOWER PRESSURE. /CARBONIC ANHYDRASE INHIBITORS/

---

Therapeutic Uses
Carbonic Anhydrase Inhibitors; Diuretics
.../USED FOR/ ADJUNCTIVE TREATMENT OF CHRONIC SIMPLE (OPEN-ANGLE) GLAUCOMA, SECONDARY GLAUCOMA, & PREOPERATIVELY IN ACUTE ANGLE-CLOSURE GLAUCOMA TO LOWER INTRAOCULAR PRESSURE PRIOR TO SURGERY.
EFFECTIVE DOSE APPEARS TO VARY FROM 125 TO 1000 MG/DAY, GIVEN ORALLY IN DIVIDED DOSES.
MEDICATION (VET): AS DIURETIC IN MILD CONGESTIVE CARDIAC EDEMAS.
For more Therapeutic Uses (Complete) data for ETHOXZOLAMIDE (6 total), please visit the HSDB record page.

---

Drug Warnings
... CARBONIC ANHYDRASE INHIBITORS SHOULD BE USED CAUTIOUSLY IN PATIENTS WITH OBSTRUCTIVE PULMONARY DISEASE BECAUSE THEY MAY PRECIPITATE ACUTE RESP FAILURE. /CARBONIC ANHYDRASE INHIBITORS/
SINCE CARBONIC ANHYDRASE INHIBITORS MAY HAVE TERATOGENIC EFFECTS, THESE DRUGS SHOULD BE AVOIDED DURING EARLY PREGNANCY. /CARBONIC ANHYDRASE INHIBITORS/
CARBONIC ANHYDRASE INHIBITORS ALSO ARE ADMINISTERED FOR PREOPERATIVE TREATMENT OF ACUTE ANGLE-CLOSURE AND CONGENITAL GLAUCOMAS. ... mORE THAN 50% OF PATIENTS ... MUST DISCONTINUE THERAPY BECAUSE OF ADVERSE REACTIONS. ... OSMOTIC AGENTS ARE USED TO REDUCE INTRAOCULAR PRESSURE AND VITREOUS VOLUME RAPIDLY PRIOR TO IRIDECTOMY AND OTHER OCULAR SURGICAL PROCEDURES. /CARBONIC ANHYDRASE INHIBITORS/
RENAL COLIC, HEMATURIA & OLIGURIA OR ANURIA MAY OCCUR DURING PROLONGED THERAPY... CARBONIC ANHYDRASE INHIBITORS REDUCE URIC ACID EXCRETION & INCR BLOOD URIC ACID LEVEL. ... HYPERURICEMIA IS USUALLY ASYMPTOMATIC BUT RARELY HAS LED TO AN EXACERBATION OF GOUT. /CARBONIC ANHYDRASE INHIBITORS/
For more Drug Warnings (Complete) data for ETHOXZOLAMIDE (7 total), please visit the HSDB record page.

---

Pharmacodynamics
Ethoxzolamide is an inhibitor of the carbonic anhydrase enzyme in proximal renal tubules that works by decreasing the reabsorption of water, sodium, potassium, bicarbonate. It also decreases the activity of carbonic anhydrase expressed in the CNS, which leads to increased seizure threshold. Inhibition of carbonic anhydrase in the eye contributes to its effect of reducing intraocular pressure and decreasing aqueous humor.

C9H10N2O3S2

258.3173

258.013

452-35-7

3295

White to off-white solid powder

1.47g/cm3

464.9ºC at 760mmHg

190-193ºC(lit.)

235ºC

8.05E-09mmHg at 25°C

1.644

3.123

1

6

3

16

341

0

OUZWUKMCLIBBOG-UHFFFAOYSA-N

InChI=1S/C9H10N2O3S2/c1-2-14-6-3-4-7-8(5-6)15-9(11-7)16(10,12)13/h3-5H,2H2,1H3,(H2,10,12,13)

6-ethoxy-1,3-benzothiazole-2-sulfonamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~387.12 mM)
H2O : ~1 mg/mL (~3.87 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (8.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.08 mg/mL (8.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.08 mg/mL (8.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)