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 Complexity of Aging: Cancer Risk Among Elderly People and Infectious Risk Among Those with Cancer
Anti-Cancer Agents in Medicinal Chemistry Diterpenes: A Therapeutic Promise for Cardiovascular Diseases
Recent Patents on Cardiovascular Drug Discovery Editorial from Editor-in-Chief: Amniotic Pulmonary Embolism and the Respiratory System: Management Trends and Future Options
Current Respiratory Medicine Reviews Clinical and Forensic Aspects of Pharmacobezoars
Current Drug Research Reviews Neurological Aspects of Medical Use of Cannabidiol
CNS & Neurological Disorders - Drug Targets An Efficient Synthesis of 7,11-diarylspiro[5.5]undecane-1,9-dione by the Michael Condensation Under Ultrasound Irradiation in Aqueous and Organic Two Phase in the Presence of Phase-Transfer Catalyst
Letters in Organic Chemistry Current Landscape of Natural Products against Coronaviruses: Perspectives in COVID-19 Treatment and Anti-viral Mechanism
Current Pharmaceutical Design Antiatherosclerotic and Cardioprotective Effects of Time-Released Garlic Powder Pills
Current Pharmaceutical Design Quassinoids: From Traditional Drugs to New Cancer Therapeutics
Current Medicinal Chemistry Editorial from Editor-in-Chief (Thrombolytic and Catheter-Directed Therapy for Pulmonary Embolism: The Paradox of Clinical Outcomes and Theory)
Current Respiratory Medicine Reviews Bleeding and Acute Coronary Syndromes: Defining, Predicting, and Managing Risk and Outcomes
Current Drug Targets Oyster Mushroom Laccase Inhibits Hepatitis C Virus Entry into Peripheral Blood Cells and Hepatoma Cells
Protein & Peptide Letters Cardio-Vascular Risks Associated with Clozapine Treatment
Current Psychiatry Reviews Is There a Place for Off-Label Pharmacotherapy in Cannabis Use Disorder? A Review on Efficacy and Safety
Current Pharmaceutical Design Inflammation and Anemia
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Cardiac ATP-Sensitive Potassium Channels: A Potential Target for an Anti-Ischaemic Pharmacological Strategy
Cardiovascular & Hematological Agents in Medicinal Chemistry Drug Repositioning: A Smart Approach for Combating SARS-CoV-2
Anti-Infective Agents An Overview of Neolignans of the Genus Piper L.: Isolation Methods and Biological Activities
Mini-Reviews in Medicinal Chemistry Practical Review of Mechanical Ventilation in Adults and Children in the Operating Room and Emergency Department
Reviews on Recent Clinical Trials Healthy Properties of Garlic
Current Nutrition & Food Science