Carbonic anhydrase inhibition and the management of glaucoma: a literature and patent review 2013-2019

ABSTRACT

Introduction: Glaucoma affects more than 70 million people worldwide. One of the major therapeutic options for its management is based on the inhibition of the metalloenzyme carbonic anhydrases (CAs, EC 4.2.1.1). CA inhibitors (CAIs) diminish ocular hypertension in glaucomatous patients by reducing the rate of bicarbonate formation and thus, the secretion of the aqueous humor.

Areas covered: This review is intended to cover the major contributions in terms of patent literature reports for the treatment of ophthalmic diseases by means of CAIs in a time frame spanning from 2013 to date.

Expert opinion: The patent literature is dominated by innovative pharmaceutical formulations including a CAI alone or in combination with other therapeutic agents. Very few novelties within drug discovery are currently present and they mainly account for new CAI moieties and classical CAIs merged into scaffolds bearing additional chemical functionalities beneficial for the pharmacological treatment of the disease. It is reasonable to expect that in the near future the so-called ‘old drugs’ will achieve pharmacological performances in the management of ocular hypertension beyond any expectations and thus open a new era of drug repurposing merely based on material science advancements.

KEYWORDS:

• Glaucoma
• carbonic anhydrase
• carbonic anhydrase inhibitors
• ophthalmic diseases

Article highlights

• Glaucoma consists of a group of progressive neuropathies characterized by a slow and progressive degeneration of retinal ganglion cells and their axons.

• The use of CAIs still represents the first choice in the therapeutic management of ocular hypertension in such a disease.

• Old CAI drugs still dominate the scene in glaucoma and no relevant novelties are currently present.

• Strong advancements into the technological and material fields allow the classical CAIs to achieve unexpected therapeutic performances.

• Latest contributions in Medicinal Chemistry report the use of potential CAI-based drugs merged with additional moieties with the intent to tackle glaucoma symptoms by means of the polypharmacological approach.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This project was partially supported by the Deanship of Scientific Research at Prince Sattam bin Abdulaziz University under the research project number 2016/03/6824.