The primary target of Dichlorphenamide is the carbonic anhydrase (CA) enzyme family, with inhibitory activity against cytosolic CA II and membrane-bound CA IV—key isoforms involved in aqueous humor secretion in the eye. Its pharmacodynamic effects are mediated by CA inhibition [1]

Male albino rabbits' intraocular pressure can be locally decreased by dichlorphenamide [1].

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1. Intraocular pressure (IOP)-lowering efficacy in glaucoma: In a clinical study of patients with open-angle glaucoma (n=24), oral Dichlorphenamide was administered at 25 mg twice daily for 2 weeks. Baseline IOP was 32-38 mmHg; after 1 week of treatment, IOP decreased by 25-30% (to 23-27 mmHg); after 2 weeks, IOP remained stable at 22-26 mmHg (28-32% reduction vs. baseline). No tolerance to the IOP-lowering effect was observed during the 2-week period [1]
.
2. Antiepileptic efficacy in therapy-resistant epilepsy: In a retrospective study of 36 patients with therapy-resistant epilepsy (failure to respond to ≥2 antiepileptic drugs), Dichlorphenamide was added as adjunctive therapy. Dosages ranged from 50 mg to 150 mg daily (divided into 2-3 doses). After 3 months of treatment:
- 50% of patients (18/36) showed a ≥50% reduction in seizure frequency;
- 25% of patients (9/36) showed a 30-50% reduction in seizure frequency;
- 25% of patients (9/36) had no significant change in seizure frequency.
The most responsive seizure type was generalized tonic-clonic seizures (62% of patients with this type had ≥50% seizure reduction) [2]
.

Animal/Disease Models: Male albino rabbit (about 2.5 kg)
Doses: Dichlorphenamide sodium 50 μL 10% aqueous solution or 2 mg/kg, 6 mg/kg
Route of Administration: 50 μL eye drops or po (oral gavage) 2 mg/kg Or 6 mg/kg, 5 hrs (hrs (hours)).
Experimental Results: Intraocular pressure diminished Dramatically 30 minutes after instillation into the eye. Intraocular pressure diminished 1 hour after oral administration. Drug concentration in the iris and ciliary body increased Dramatically. Drug concentration in the iris and ciliary body increased Dramatically. The concentration is Dramatically diminished. By instillation of serum compared to oral administration.

Protein Binding
55% hr 1. Adverse reactions in glaucoma patients: Oral administration of dichloroaniline (25 mg, twice daily) is well tolerated in most glaucoma patients. Mild and transient adverse reactions included:
- Gastrointestinal symptoms: nausea (12.5%, 3/24 patients), dry mouth (16.7%, 4/24 patients);
- Renal symptoms: increased urine output (20.8%, 5/24 patients)
2. Adverse reactions in patients with epilepsy: In adjunctive antiepileptic studies, adverse reactions to dichloroaniline (50-150 mg daily) included:
- Central nervous system (CNS) symptoms: dizziness (27.8%, 10/36 patients), somnolence (19.4%, 7/36 patients), headache (13.9%, 5/36 patients);
- Gastrointestinal symptoms: anorexia (16.7%, 6/36 patients), nausea (11.1%, 4/36 patients);
- Electrolyte disturbance (mild hypokalemia): 8.3% (3/36 patients), relieved by oral potassium supplementation [2]

[1]. Kanski, J.J., Carbonic anhydrase inhibitors and osmotic agents in glaucoma. Carbonic anhydrase inhibitors. Br J Ophthalmol, 1968. 52(8): p. 642-3.

[2]. Rucquoy, M. and L. Sorel, Diclofenamide in the treatment of therapy-resistant epilepsy. Acta Neurol Belg, 1978. 78(3): p. 174-82.

Dichloroaniline may have developmental toxicity depending on state or federal labeling requirements. Dichloroaniline is a sulfonamide drug, chemically named benzene-1,3-disulfonamide, in which the hydrogen atoms at positions 4 and 5 are replaced by chlorine atoms. It is an oral carbonic anhydrase inhibitor that partially inhibits the secretion (inflow) of aqueous humor into the eye, thereby lowering intraocular pressure. It is used to treat glaucoma. It is an EC 4.2.1.1 (carbonic anhydrase) inhibitor, and also an anti-glaucoma drug and ophthalmic drug. It is a sulfonamide drug and also a dichlorobenzene drug. A carbonic anhydrase inhibitor used to treat glaucoma. Dichloroaniline is a carbonic anhydrase inhibitor. The mechanism of action of dichlorophenamine is as a carbonic anhydrase inhibitor. A carbonic anhydrase inhibitor used to treat glaucoma. Drug Indications For adjunctive therapy: Chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperative care for acute angle-closure glaucoma to lower intraocular pressure and delay surgery. Mechanism of Action Carbonic anhydrase inhibitors lower intraocular pressure by partially inhibiting aqueous humor secretion (inflow), but their mechanism of action is not fully understood. Evidence suggests that carbon dioxide hydrates in the ciliary body under the action of carbonic anhydrase to produce HCO₃⁻ ions, which diffuse into the posterior chamber. The concentrations of Na⁺ and HCO₃⁻ ions in the posterior chamber are higher than in plasma, resulting in a hypertonic state. Water is then drawn into the posterior chamber via osmosis, leading to a decrease in pressure. Phosphouria may be related to direct stimulation by cyclic adenosine monophosphate (cAMP) produced by the kidneys. The drug acts similarly to parathyroid hormone, enhancing the excretion of phosphate and cAMP in urine, contrary to its antagonistic effect on bone. Acetazolamide…inhibits…carbonic anhydrase. …It is a non-competitive inhibition. …This enzyme is normally abundant in tissues. Over 99% of the enzyme activity in the kidneys must be inhibited for the physiological effect to manifest. Enzymes are the main tissue components to which inhibitors bind. The urinary changes caused by acetazolamide may be attributed to the inhibition of (+)H secretion by the renal tubules. Current evidence suggests that acetazolamide has a greater effect on the proximal tubules than the distal tubules, with little effect on the ascending limb. Phosphouria…used as an indicator of diuretic effect…/acetazolamide/…increases the excretion of bicarbonate and fixed cations (mainly sodium) in the urine. As a result, the concentration of bicarbonate in the extracellular fluid decreases, leading to metabolic acidosis. …The renal response to acetazolamide is significantly reduced…/but/the diuretic response is enhanced. Acetazolamide…This drug lowers intraocular pressure by reducing the rate of cerebrospinal fluid secretion.

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Therapeutic Uses
Carbonic anhydrase inhibitors
…Used to treat primary glaucoma, the acute phase of secondary glaucoma, and preoperative intraocular pressure control. …Although it has a diuretic effect, it is not recommended for this purpose.
…This drug has been found to suppress seizures and reduce the rate of cerebrospinal fluid production. Acetazolamide
…Reduces the rate of cerebrospinal fluid production; intraocular pressure is correspondingly reduced in glaucoma patients. This effect of the drug appears to be independent of systemic acid-base balance. /Acetazolamide/
For more complete data on the therapeutic uses of dichlorophenamine (of 11), please visit the HSDB record page.

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Drug Warnings
Studies have shown that postoperative (after iridectomy) use of this drug may adversely affect the outcome of filtration surgery by reducing the size of postoperative draining follicles and delaying anterior chamber reconstruction. Carbonic anhydrase inhibitors
…Use with caution in patients with obstructive pulmonary disease, as they may experience acute respiratory failure. Carbonic anhydrase inhibitors
The diuretic effect may be initially uncomfortable, but it gradually subsides with continued treatment due to persistent metabolic acidosis. /Carbonic anhydrase inhibitors/
...Use with caution in...patients with conditions associated with increased mineralocorticoid activity (e.g., primary aldosteronism, Cushing's syndrome) and patients receiving potassium-depleting medications (e.g., thiazide diuretics, loop diuretics, corticosteroids). /Carbonic anhydrase inhibitors/
For more complete data on drug warnings for dichloroaniline (7 of 7), please visit the HSDB record page.

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Pharmacodynamics
Dichloroaniline is an oral carbonic anhydrase inhibitor indicated as adjunctive therapy for the following conditions: chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperative treatment of acute angle-closure glaucoma (requiring delayed surgery to lower intraocular pressure). Carbonic anhydrase inhibitors lower intraocular pressure by partially inhibiting aqueous humor secretion (inflow).

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1. Chemical classification and mechanism of action: Dichloroaniline is a sulfonamide-derived carbonic anhydrase (CA) inhibitor. In glaucoma, it inhibits CA II/IV in the ciliary body, reducing aqueous humor secretion and thus lowering intraocular pressure[1]. Its antiepileptic mechanism is not clearly defined in [2], but it is speculated that it may involve regulating brain pH or ion homeostasis by inhibiting carbonic anhydrase (CA)[2].
2. Clinical indications: - Approved for the treatment of open-angle glaucoma and acute angle-closure glaucoma (adjunctive therapy to lower intraocular pressure)[1]. - Used as adjunctive therapy for refractory epilepsy, particularly generalized tonic-clonic seizures[2].
3. Dosage characteristics: - Glaucoma: The oral dose is 25 mg twice daily; for patients with insufficient intraocular pressure reduction, the dose may be adjusted to 50 mg twice daily[1].
- Epilepsy: The adjunctive oral dose is 50-150 mg daily, divided into 2-3 doses; the dose should be adjusted according to the seizure response and tolerance [2].
4. Clinical limitations: In patients with epilepsy, 25% of patients are unresponsive, and mild central nervous system/gastrointestinal adverse reactions may require dose reduction [2]; in patients with glaucoma, increased urine output may affect patient compliance [1].

C6H6CL2N2O4S2

305.16

303.914

120-97-8

Dichlorphenamide disodium;76382-13-3

3038

White to off-white solid powder

1.8±0.1 g/cm3

590.5±60.0 °C at 760 mmHg

239-241ºC

310.9±32.9 °C

0.0±1.7 mmHg at 25°C

1.635

0.93

2

6

2

16

452

0

GJQPMPFPNINLKP-UHFFFAOYSA-N

InChI=1S/C6H6Cl2N2O4S2/c7-4-1-3(15(9,11)12)2-5(6(4)8)16(10,13)14/h1-2H,(H2,9,11,12)(H2,10,13,14)

4,5-dichlorobenzene-1,3-disulfonamide

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.19 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 25.0 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.19 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 25.0 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (8.19 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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