Brinzolamide
[CAS# 138890-62-7]

Identification

• Classification: Biochemical >> Inhibitor >> Metabolism >> Carbonic anhydrase inhibitor
• Name: Brinzolamide
• Synonyms: (R)-4-(Ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide
• Molecular Formula: C₁₂H₂₁N₃O₅S₃
• Molecular Weight: 383.51
• CAS Registry Number: 138890-62-7
• EC Number: 620-511-8
• SMILES: CCN[C@H]1CN(S(=O)(=O)C2=C1C=C(S2)S(=O)(=O)N)CCCOC

Properties

• Solubility: DMSO >10 mg/mL (Expl.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302
• Precautionary Statements: P264-P270-P301+P317-P330-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332

Discovory and Applicatios

Brinzolamide is a carbonic anhydrase inhibitor used in ophthalmology to lower elevated intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. It is a sulfonamide derivative that acts by inhibiting carbonic anhydrase II (CA-II), an enzyme found in the ciliary body epithelium of the eye. Inhibition of CA-II reduces the formation of bicarbonate ions, leading to decreased sodium and fluid transport, and ultimately lowers aqueous humor production. The reduction in aqueous humor decreases IOP, which is a critical factor in the progression of glaucomatous optic nerve damage.

Brinzolamide was developed following the success of earlier carbonic anhydrase inhibitors, such as acetazolamide and dorzolamide. However, brinzolamide was specifically designed for topical administration, offering a more favorable side effect profile than systemic agents, and with a more comfortable pH than dorzolamide. The compound was introduced to clinical practice under the trade name Azopt and was approved by the U.S. Food and Drug Administration (FDA) in 1998 for ophthalmic use.

Brinzolamide is formulated as a 1% ophthalmic suspension and is typically administered as one drop in the affected eye(s) two to three times daily. It may be used as monotherapy or in combination with other IOP-lowering agents, such as beta-adrenergic antagonists or prostaglandin analogs. A fixed-dose combination of brinzolamide with timolol maleate (marketed as Simbrinza in some regions) was also developed to enhance treatment adherence and convenience by reducing the number of daily administrations.

Clinical studies have demonstrated that brinzolamide effectively reduces intraocular pressure with efficacy comparable to dorzolamide, and with similar safety. It is especially beneficial in patients who are intolerant or unresponsive to other classes of IOP-lowering medications. The peak IOP-lowering effect occurs approximately two to four hours after administration, with a duration of action sufficient to support dosing every 8 to 12 hours.

As with other topical carbonic anhydrase inhibitors, brinzolamide may cause ocular side effects, including blurred vision, bitter taste, eye discomfort, and foreign body sensation. Systemic absorption is minimal, but adverse reactions such as headache, dry mouth, and fatigue have been reported in rare cases. Because brinzolamide is a sulfonamide, caution is advised in patients with known hypersensitivity to sulfonamide-derived drugs. The drug is contraindicated in patients with severe renal impairment due to its renal excretion and the risk of systemic accumulation.

Pharmacokinetically, brinzolamide exhibits good corneal penetration and achieves therapeutic concentrations in ocular tissues. Its protein binding and intraocular accumulation contribute to sustained enzyme inhibition. Brinzolamide is eliminated primarily through the kidneys, and steady-state levels may be reached after repeated administration.

Brinzolamide's role in the management of glaucoma and ocular hypertension has been well established, particularly for patients requiring combination therapy or who cannot tolerate first-line agents. It remains a key component of individualized treatment strategies aimed at preserving visual function and preventing progression of glaucomatous optic neuropathy.

In summary, brinzolamide is a topically applied carbonic anhydrase inhibitor used to lower intraocular pressure in glaucoma and ocular hypertension. Developed for improved ocular tolerability and effectiveness, it serves as an important therapeutic option, either alone or in combination with other medications, in the long-term management of these chronic eye diseases.

References

1998. Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: Molecular basis of isozyme-drug discrimination. Protein Science, 7(3).
DOI: 10.1002/pro.5560070303

2022. Mucoadhesive brinzolamide-loaded nanofibers for alternative glaucoma treatment. European Journal of Pharmaceutics and Biopharmaceutics, 180.
DOI: 10.1016/j.ejpb.2022.09.008

2024. Fabrication of architectonic nanosponges for intraocular delivery of Brinzolamide: An insight into QbD driven optimization, in vitro characterization, and pharmacodynamics. International Journal of Pharmaceutics, 651.
DOI: 10.1016/j.ijpharm.2023.123746