Abstract
Carbonic anhydrase inhibitors (CAIs) such as acetazolamide, methazolamide, ethoxzolamide and dichlorophenamide were and still are widely used systemic antiglaucoma drugs. Their mechanism of action consists in inhibition of CA isozymes present in ciliary processes of the eye (such as CA II, IV and XII), with the consequent reduction of bicarbonate and aqueous humour secretion, and of elevated intraocular pressure (IOP) characteristic of this disease. Since CA II/IV/XII are present in many other tissues/organs, generally, systemic CAIs possess undesired side effects such as numbness and tingling of extremities; metallic taste; depression; fatigue; malaise; weight loss; decreased libido; gastrointestinal irritation; metabolic acidosis; renal calculi and transient myopia. In order to avoid these undesired side effects, recently, topically effective CAIs have been developed. Two drugs are available clinically: dorzolamide and brinzolamide. Both these drugs are applied topically as water solutions/suspensions, alone or in combination with other agents (such as β- blockers, prostaglandin derivatives, etc) and produce a consistent and prolonged reduction of IOP. Furthermore, recent reports show both the systemically as well as topically acting sulfonamide CAIs to be effective in the treatment of macular oedema and other macular degeneration diseases, for which pharmacological treatment was unavailable up to now. Much research is in act in the search of even more effective topically acting CAIs, free of the inconveniences and side effects of the presently available drugs. For achieving this goal, a recently reported strategy, the tail approach, was extensively applied for the synthesis of large numbers of derivatives possessing various physico-chemical properties. Many such new sulfonamides showed promising antiglaucoma activity in animal models of the disease.
Keywords: high intraocular pressure, age-related macular degeneration, acetazolamide, macular edema, brinzolamide hydrochloride
Current Topics in Medicinal Chemistry
Title: The Development of Topically Acting Carbonic Anhydrase Inhibitors as Antiglaucoma Agents
Volume: 7 Issue: 9
Author(s): Francesco Mincione, Andrea Scozzafava and Claudiu T. Supuran
Affiliation:
Keywords: high intraocular pressure, age-related macular degeneration, acetazolamide, macular edema, brinzolamide hydrochloride
Abstract: Carbonic anhydrase inhibitors (CAIs) such as acetazolamide, methazolamide, ethoxzolamide and dichlorophenamide were and still are widely used systemic antiglaucoma drugs. Their mechanism of action consists in inhibition of CA isozymes present in ciliary processes of the eye (such as CA II, IV and XII), with the consequent reduction of bicarbonate and aqueous humour secretion, and of elevated intraocular pressure (IOP) characteristic of this disease. Since CA II/IV/XII are present in many other tissues/organs, generally, systemic CAIs possess undesired side effects such as numbness and tingling of extremities; metallic taste; depression; fatigue; malaise; weight loss; decreased libido; gastrointestinal irritation; metabolic acidosis; renal calculi and transient myopia. In order to avoid these undesired side effects, recently, topically effective CAIs have been developed. Two drugs are available clinically: dorzolamide and brinzolamide. Both these drugs are applied topically as water solutions/suspensions, alone or in combination with other agents (such as β- blockers, prostaglandin derivatives, etc) and produce a consistent and prolonged reduction of IOP. Furthermore, recent reports show both the systemically as well as topically acting sulfonamide CAIs to be effective in the treatment of macular oedema and other macular degeneration diseases, for which pharmacological treatment was unavailable up to now. Much research is in act in the search of even more effective topically acting CAIs, free of the inconveniences and side effects of the presently available drugs. For achieving this goal, a recently reported strategy, the tail approach, was extensively applied for the synthesis of large numbers of derivatives possessing various physico-chemical properties. Many such new sulfonamides showed promising antiglaucoma activity in animal models of the disease.
Export Options
About this article
Cite this article as:
Mincione Francesco, Scozzafava Andrea and Supuran T. Claudiu, The Development of Topically Acting Carbonic Anhydrase Inhibitors as Antiglaucoma Agents, Current Topics in Medicinal Chemistry 2007; 7 (9) . https://dx.doi.org/10.2174/156802607780636735
DOI https://dx.doi.org/10.2174/156802607780636735 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Role of Growth Factors in the Prevention and Treatment of Chemotherapy-Induced Peripheral Neurotoxicity
Current Drug Safety Future Directions in the Treatment of Neuropathic Pain: A Review on Various Therapeutic Targets
CNS & Neurological Disorders - Drug Targets Editorial: Pharmacological Therapy to Prevent Sudden Cardiac Death: Indications and Limitations in the Era of Devices
Mini-Reviews in Medicinal Chemistry Management of Acute Aluminum Phosphide Poisoning: Has Anything Changed?
Drug Metabolism Letters Triphala in Prevention of Dental Caries and as an Antimicrobial in Oral Cavity- A Review
Infectious Disorders - Drug Targets Early Cerebral Infarction Following Aneurysmal Subarachnoid Hemorrhage: Frequency, Risk Factors, Patterns, and Prognosis
Current Neurovascular Research Obesity-Induced Cerebral Hypoperfusion Derived from Endothelial Dysfunction: One of the Risk Factors for Alzheimer's Disease
Current Alzheimer Research An Improved Synthesis of m-Hydroxymexiletine, a Potent Mexiletine Metabolite
Drug Metabolism Letters Renin-Angiotensin Antagonists: Therapeutic Effects Beyond Blood Pressure Control?
Current Pharmaceutical Design Discovery and Advancement of Farnesyl Transferase Inhibitors as Potential Anticancer Therapeutic Agents: SCH 66336 a Case Study
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents High Sensitivity Troponin in Cardiovascular Disease. Is There More Than a Marker of Myocardial Death?
Current Topics in Medicinal Chemistry Study of Convolvulus pluricaulis for Antioxidant and Anticonvulsant Activity
Central Nervous System Agents in Medicinal Chemistry Discovery of Natural Product-Derived 5-HT1A Receptor Binders by Cheminfomatics Modeling of Known Binders, High Throughput Screening and Experimental Validation
Combinatorial Chemistry & High Throughput Screening Urotensin II: A Vascular Mediator in Health and Disease
Current Vascular Pharmacology A Pilot Study to Assess Adenosine 5’-triphosphate Metabolism in Red Blood Cells as a Drug Target for Potential Cardiovascular Protection
Cardiovascular & Hematological Disorders-Drug Targets Phosphodiesterase Inhibition as a Therapeutic Target for Brain Ischemia
CNS & Neurological Disorders - Drug Targets Activated Carbon/MoO<sub>3</sub>: Efficient Catalyst for Green Synthesis of Chromeno[<i>d</i>]pyrimidinediones and Xanthenones
Combinatorial Chemistry & High Throughput Screening Treatment of Diabetic Foot Ulcers
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Role of Renin Angiotensin System Inhibitors in Cardiovascular and Renal Protection: A Lesson from Clinical Trials
Current Pharmaceutical Design Thrombolysis in Ischemic Stroke: Focus on New Treatment Strategies
Recent Patents on Cardiovascular Drug Discovery