carbonic anhydrase inhibitors

Summary

Summary: A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES.

Top Publications

  1. Ganesh A, Stroh E, Manayath G, Al Zuhaibi S, Levin A. Macular cysts in retinal dystrophy. Curr Opin Ophthalmol. 2011;22:332-9 pubmed publisher
    ..cysts in retinal dystrophy, differentiate it from cystoid macular edema (CME), and review the role of carbonic anhydrase inhibitors in management...
  2. Yang M, Chien W, Lu D, Liou H, Fu W. Acetazolamide impairs fear memory consolidation in rodents. Neuropharmacology. 2013;67:412-8 pubmed publisher
    ..In clinical practice, clinicians should be aware of this side effect in patients taking AZ. In addition, this inhibition of fear memory by AZ could potentially be applied to patients with posttraumatic stress disorder. ..
  3. Kayser B, Dumont L, Lysakowski C, Combescure C, Haller G, Tramer M. Reappraisal of acetazolamide for the prevention of acute mountain sickness: a systematic review and meta-analysis. High Alt Med Biol. 2012;13:82-92 pubmed publisher
    ..The degree of efficacy of acetazolamide for the prevention of AMS is limited when the baseline risk is low, and there is some evidence of dose-responsiveness...
  4. Monti S, Supuran C, De Simone G. Anticancer carbonic anhydrase inhibitors: a patent review (2008 - 2013). Expert Opin Ther Pat. 2013;23:737-49 pubmed publisher
  5. Scozzafava A, Supuran C, Carta F. Antiobesity carbonic anhydrase inhibitors: a literature and patent review. Expert Opin Ther Pat. 2013;23:725-35 pubmed publisher
    ..literature regarding obesity or obesity-related pathologies, being particularly focused on the use of carbonic anhydrase inhibitors (CAI) such as TPM and ZNS which inhibit the de novo lipogenesis...
  6. Fogagnolo P, Centofanti M, Figus M, Frezzotti P, Fea A, Ligorio P, et al. Short-term changes in intraocular pressure after phacoemulsification in glaucoma patients. Ophthalmologica. 2012;228:154-8 pubmed
    ..The use of systemic acetazolamide provided significant control of IOP and could be considered a 'possible standard' management of cataract surgery in POAG patients. ..
  7. Seupaul R, Welch J, Malka S, Emmett T. Pharmacologic prophylaxis for acute mountain sickness: a systematic shortcut review. Ann Emerg Med. 2012;59:307-317.e1 pubmed publisher
    ..Since 2000, a number of other agents have been reported to be beneficial. This EBEM review evaluates the most current evidence on this topic...
  8. Scozzafava A, Supuran C. Glaucoma and the applications of carbonic anhydrase inhibitors. Subcell Biochem. 2014;75:349-59 pubmed publisher
    ..CAIs are used alone or in combination with other drugs such as adrenergic agonist/antagonists, or PG analogs, being an important component of the antiglaucoma drugs armamentarium. ..
  9. McKenna R, Supuran C. Carbonic anhydrase inhibitors drug design. Subcell Biochem. 2014;75:291-323 pubmed publisher
    ..Promising compounds that inhibit CAs from bacterial and fungal pathogens, of the dithiocarbamate, phenol and carboxylate types have also been reported. ..
  10. Neri D, Supuran C. Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov. 2011;10:767-77 pubmed publisher
    ..These antitumour mechanisms are not exploited by the classical cancer drugs and therefore represent a new anticancer drug discovery strategy. ..

Detail Information

Publications62

  1. Ganesh A, Stroh E, Manayath G, Al Zuhaibi S, Levin A. Macular cysts in retinal dystrophy. Curr Opin Ophthalmol. 2011;22:332-9 pubmed publisher
    ..cysts in retinal dystrophy, differentiate it from cystoid macular edema (CME), and review the role of carbonic anhydrase inhibitors in management...
  2. Yang M, Chien W, Lu D, Liou H, Fu W. Acetazolamide impairs fear memory consolidation in rodents. Neuropharmacology. 2013;67:412-8 pubmed publisher
    ..In clinical practice, clinicians should be aware of this side effect in patients taking AZ. In addition, this inhibition of fear memory by AZ could potentially be applied to patients with posttraumatic stress disorder. ..
  3. Kayser B, Dumont L, Lysakowski C, Combescure C, Haller G, Tramer M. Reappraisal of acetazolamide for the prevention of acute mountain sickness: a systematic review and meta-analysis. High Alt Med Biol. 2012;13:82-92 pubmed publisher
    ..The degree of efficacy of acetazolamide for the prevention of AMS is limited when the baseline risk is low, and there is some evidence of dose-responsiveness...
  4. Monti S, Supuran C, De Simone G. Anticancer carbonic anhydrase inhibitors: a patent review (2008 - 2013). Expert Opin Ther Pat. 2013;23:737-49 pubmed publisher
  5. Scozzafava A, Supuran C, Carta F. Antiobesity carbonic anhydrase inhibitors: a literature and patent review. Expert Opin Ther Pat. 2013;23:725-35 pubmed publisher
    ..literature regarding obesity or obesity-related pathologies, being particularly focused on the use of carbonic anhydrase inhibitors (CAI) such as TPM and ZNS which inhibit the de novo lipogenesis...
  6. Fogagnolo P, Centofanti M, Figus M, Frezzotti P, Fea A, Ligorio P, et al. Short-term changes in intraocular pressure after phacoemulsification in glaucoma patients. Ophthalmologica. 2012;228:154-8 pubmed
    ..The use of systemic acetazolamide provided significant control of IOP and could be considered a 'possible standard' management of cataract surgery in POAG patients. ..
  7. Seupaul R, Welch J, Malka S, Emmett T. Pharmacologic prophylaxis for acute mountain sickness: a systematic shortcut review. Ann Emerg Med. 2012;59:307-317.e1 pubmed publisher
    ..Since 2000, a number of other agents have been reported to be beneficial. This EBEM review evaluates the most current evidence on this topic...
  8. Scozzafava A, Supuran C. Glaucoma and the applications of carbonic anhydrase inhibitors. Subcell Biochem. 2014;75:349-59 pubmed publisher
    ..CAIs are used alone or in combination with other drugs such as adrenergic agonist/antagonists, or PG analogs, being an important component of the antiglaucoma drugs armamentarium. ..
  9. McKenna R, Supuran C. Carbonic anhydrase inhibitors drug design. Subcell Biochem. 2014;75:291-323 pubmed publisher
    ..Promising compounds that inhibit CAs from bacterial and fungal pathogens, of the dithiocarbamate, phenol and carboxylate types have also been reported. ..
  10. Neri D, Supuran C. Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov. 2011;10:767-77 pubmed publisher
    ..These antitumour mechanisms are not exploited by the classical cancer drugs and therefore represent a new anticancer drug discovery strategy. ..
  11. Genead M, McAnany J, Fishman G. Topical dorzolamide for treatment of cystoid macular edema in patients with choroideremia. Retina. 2012;32:826-33 pubmed publisher
    ..To determine the value of a topical carbonic anhydrase inhibitor on the macular thickness and function in choroideremia patients with cystoid macular edema...
  12. Carta F, Scozzafava A, Supuran C. Sulfonamides: a patent review (2008 - 2012). Expert Opin Ther Pat. 2012;22:747-58 pubmed publisher
    ..This privileged structural motif is likely to be present in other drugs in the future. ..
  13. Ikeda Y, Hisatomi T, Yoshida N, Notomi S, Murakami Y, Enaida H, et al. The clinical efficacy of a topical dorzolamide in the management of cystoid macular edema in patients with retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol. 2012;250:809-14 pubmed publisher
    ..The results demonstrated that a topical dorzolamide is effective for the treatment of CME in patients with RP, and that the positive treatment effects last for up to 6 months. ..
  14. Agrawal V, Bano S, Supuran C, Khadikar P. QSAR study on carbonic anhydrase inhibitors: aromatic/heterocyclic sulfonamides containing 8-quinoline-sulfonyl moieties, with topical activity as antiglaucoma agents. Eur J Med Chem. 2004;39:593-600 pubmed
    ..Excellent results are obtained against all the three isozymes; CA I, II and IV of the zinc enzyme CA by using indicator parameters along with (1)chi(v). ..
  15. Innocenti A, Winum J, Hall R, Muhlschlegel F, Scozzafava A, Supuran C. Carbonic anhydrase inhibitors. Inhibition of the fungal beta-carbonic anhydrases from Candida albicans and Cryptococcus neoformans with boronic acids. Bioorg Med Chem Lett. 2009;19:2642-5 pubmed publisher
    ..The host human enzymes CA I and II were also effectively inhibited by these boronic acids. The B(OH)(2) moiety is thus a new zinc-binding group for designing effective inhibitors of the alpha- and beta-CAs. ..
  16. Venance S, Cannon S, Fialho D, Fontaine B, Hanna M, Ptacek L, et al. The primary periodic paralyses: diagnosis, pathogenesis and treatment. Brain. 2006;129:8-17 pubmed
    ..Moreover, understanding the skeletal muscle channelopathies will hopefully lead to insights into the more common central nervous system channel diseases such as migraine and epilepsy...
  17. Chow T, Browne V, Heileson H, Wallace D, Anholm J, Green S. Ginkgo biloba and acetazolamide prophylaxis for acute mountain sickness: a randomized, placebo-controlled trial. Arch Intern Med. 2005;165:296-301 pubmed
    ..In this study, prophylactic acetazolamide therapy decreased the symptoms of AMS and trended toward reducing its incidence. We found no evidence of similar efficacy for Ginkgo biloba. ..
  18. Isik S, Kockar F, Arslan O, Guler O, Innocenti A, Supuran C. Carbonic anhydrase inhibitors. Inhibition of the beta-class enzyme from the yeast Saccharomyces cerevisiae with anions. Bioorg Med Chem Lett. 2008;18:6327-31 pubmed publisher
    ..8-55.6 mM) and strongly inhibited by bromide, iodide, and sulfamide (K(I)s of 8.7-10.8 microM). The other investigated anions showed inhibition constants in the low millimolar range...
  19. Steele R, Benedini F, Biondi S, Borghi V, Carzaniga L, Impagnatiello F, et al. Nitric oxide-donating carbonic anhydrase inhibitors for the treatment of open-angle glaucoma. Bioorg Med Chem Lett. 2009;19:6565-70 pubmed publisher
    ..Several compounds were synthesized and their activity as selective carbonic anhydrase inhibitors (CAI) evaluated in vitro on recombinant hCA type I, II and IV enzyme isoforms where they showed ..
  20. Giacomotto J, Pertl C, Borrel C, Walter M, Bulst S, Johnsen B, et al. Evaluation of the therapeutic potential of carbonic anhydrase inhibitors in two animal models of dystrophin deficient muscular dystrophy. Hum Mol Genet. 2009;18:4089-101 pubmed publisher
    ..Two of the most active hits obtained were methazolamide and dichlorphenamide, carbonic anhydrase inhibitors widely used in human therapy. In C...
  21. Supuran C, Vullo D, Manole G, Casini A, Scozzafava A. Designing of novel carbonic anhydrase inhibitors and activators. Curr Med Chem Cardiovasc Hematol Agents. 2004;2:49-68 pubmed
    ..e., CA I, II, III and IV. The possible physiologic relevance of CA activation will also be addressed, together with the recent pharmacological applications of blood CA isozymes activators, as potential memory enhancing drugs. ..
  22. Temperini C, Cecchi A, Scozzafava A, Supuran C. Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009;17:1214-21 pubmed publisher
    ..The newly evidenced binding modes of these diuretics may be exploited for designing better CA II inhibitors as well as compounds with selectivity/affinity for various isoforms with medicinal chemistry applications. ..
  23. Van Patot M, Leadbetter G, Keyes L, Maakestad K, Olson S, Hackett P. Prophylactic low-dose acetazolamide reduces the incidence and severity of acute mountain sickness. High Alt Med Biol. 2008;9:289-93 pubmed publisher
    ..Low-dose acetazolamide administered prior to ascent and on day 1 at 4300 m effectively reduced the incidence and severity of AMS in a high-risk setting. ..
  24. Apushkin M, Fishman G, Grover S, Janowicz M. Rebound of cystoid macular edema with continued use of acetazolamide in patients with retinitis pigmentosa. Retina. 2007;27:1112-8 pubmed
    ..Results from our study suggest that rebound of CME with the continued use of acetazolamide observed by OCT may occur more frequently than previously appreciated. ..
  25. Innocenti A, Scozzafava A, Supuran C. Carbonic anhydrase inhibitors. Inhibition of transmembrane isoforms IX, XII, and XIV with less investigated anions including trithiocarbonate and dithiocarbamate. Bioorg Med Chem Lett. 2010;20:1548-50 pubmed publisher
    ..12-0.66mM). N,N-Diethyldithiocarbamate was a low micromolar inhibitor also against CA XII and XIV (K(I)s of 1.0-1.1microM), suggesting that this new zinc-binding group (CS2-) may lead to efficient inhibitors targeting transmembrane CAs...
  26. Innocenti A, Leewattanapasuk W, Muhlschlegel F, Mastrolorenzo A, Supuran C. Carbonic anhydrase inhibitors. Inhibition of the beta-class enzyme from the pathogenic yeast Candida glabrata with anions. Bioorg Med Chem Lett. 2009;19:4802-5 pubmed publisher
    ..The other anions investigated showed inhibition constants in the low millimolar range, with the exception of bromide and iodide (K(I)s of 27-42 mM)...
  27. Basnyat B, Gertsch J, Holck P, Johnson E, Luks A, Donham B, et al. Acetazolamide 125 mg BD is not significantly different from 375 mg BD in the prevention of acute mountain sickness: the prophylactic acetazolamide dosage comparison for efficacy (PACE) trial. High Alt Med Biol. 2006;7:17-27 pubmed
    ..02). We conclude that 125 mg bd of acetazolamide is not significantly different from 375 mg bd in the prevention of AMS; 125 mg bd should be considered the preferred dosage when indicated for persons ascending to altitudes above 2500 m. ..
  28. Gugleta K. Topical carbonic anhydrase inhibitors and visual function in glaucoma and ocular hypertension. Curr Med Res Opin. 2010;26:1255-67 pubmed publisher
    Dorzolamide and brinzolamide are topical carbonic anhydrase inhibitors (CAI) indicated for patients with glaucoma and ocular hypertension...
  29. Feldman R, Tanna A, Gross R, Chuang A, Baker L, Reynolds A, et al. Comparison of the ocular hypotensive efficacy of adjunctive brimonidine 0.15% or brinzolamide 1% in combination with travoprost 0.004%. Ophthalmology. 2007;114:1248-54 pubmed
    ..035). The combination of travoprost and brinzolamide was statistically significantly more efficacious than the combination of travoprost and brimonidine in lowering IOP. The clinical significance of this difference is uncertain. ..
  30. Aaslid R. Cerebral autoregulation and vasomotor reactivity. Front Neurol Neurosci. 2006;21:216-28 pubmed
    ..In this chapter, the various CO2 and acetazolamide approaches that determine vasomotor reactivity are described and discussed. ..
  31. Ran X, Wang H, Chen Y, Zeng Z, Zhou Q, Zheng R, et al. Aquaporin-1 expression and angiogenesis in rabbit chronic myocardial ischemia is decreased by acetazolamide. Heart Vessels. 2010;25:237-47 pubmed publisher
    ..Our findings indicate a novel role for AQP1 in postnatal angiogenesis, which has implications in diverse pathophysiological conditions including wound healing, tumor metastasis, and organ regeneration...
  32. Pastorekova S, Zatovicova M, Pastorek J. Cancer-associated carbonic anhydrases and their inhibition. Curr Pharm Des. 2008;14:685-98 pubmed
    ..This review summarizes research data related to distribution, regulation and functional aspects of CA IX and CA XII, and describes emerging possibilities for clinical exploitation of CA inhibitors as imaging tools and anticancer drugs. ..
  33. Liu J, Medeiros F, Slight J, Weinreb R. Comparing diurnal and nocturnal effects of brinzolamide and timolol on intraocular pressure in patients receiving latanoprost monotherapy. Ophthalmology. 2009;116:449-54 pubmed publisher
    ..To compare the diurnal and nocturnal effects of brinzolamide and timolol on intraocular pressure (IOP) in patients already receiving monotherapy with latanoprost...
  34. Tricarico D, Mele A, Conte Camerino D. Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels. Neuromuscul Disord. 2006;16:39-45 pubmed
    ..The activation of Ca2+-activated-K+ channel in addition to the mild diuretic effect explained the efficacy of ACTZ and DCP in K+ -deficient rats and in familial hypokalaemic-PP. ..
  35. Li Y, Wang H, Oosterwijk E, Tu C, Shiverick K, Silverman D, et al. Expression and activity of carbonic anhydrase IX is associated with metabolic dysfunction in MDA-MB-231 breast cancer cells. Cancer Invest. 2009;27:613-23 pubmed publisher
    ..Together, these studies suggest that CAIX expression and activity is associated with metabolic dysfunction in MDA-MB-231 cells. ..
  36. Winum J, Cecchi A, Montero J, Innocenti A, Scozzafava A, Supuran C. Carbonic anhydrase inhibitors. Synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with boron-containing sulfonamides, sulfamides, and sulfamates: toward agents for boron neutron capture therapy of hypoxic. Bioorg Med Chem Lett. 2005;15:3302-6 pubmed
  37. Di Fiore A, Pedone C, D Ambrosio K, Scozzafava A, De Simone G, Supuran C. Carbonic anhydrase inhibitors: Valdecoxib binds to a different active site region of the human isoform II as compared to the structurally related cyclooxygenase II "selective" inhibitor celecoxib. Bioorg Med Chem Lett. 2006;16:437-42 pubmed
    ..These different binding modes allow for the further drug design of various CA inhibitors belonging to the benzenesulfonamide class. ..
  38. Nishimori I, Minakuchi T, Morimoto K, Sano S, Onishi S, Takeuchi H, et al. Carbonic anhydrase inhibitors: DNA cloning and inhibition studies of the alpha-carbonic anhydrase from Helicobacter pylori, a new target for developing sulfonamide and sulfamate gastric drugs. J Med Chem. 2006;49:2117-26 pubmed
    ..25-3.48, showing thus some selectivity for inhibiting the bacterial enzyme. Since hpCA is essential for the survival of the pathogen in acid, it might be used as a new pharmacologic tool in the management of drug-resistant H. pylori. ..
  39. Becker H, Klier M, Deitmer J. Nonenzymatic augmentation of lactate transport via monocarboxylate transporter isoform 4 by carbonic anhydrase II. J Membr Biol. 2010;234:125-35 pubmed publisher
  40. De Simone G, Di Fiore A, Menchise V, Pedone C, Antel J, Casini A, et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: solution and X-ray crystallographic studies. Bioorg Med Chem Lett. 2005;15:2315-20 pubmed
    ..5 A) with residues Gln92, Val121, Phe131, Leu198, Thr200, Pro202. ..
  41. Di Fiore A, Monti S, Hilvo M, Parkkila S, Romano V, Scaloni A, et al. Crystal structure of human carbonic anhydrase XIII and its complex with the inhibitor acetazolamide. Proteins. 2009;74:164-75 pubmed publisher
  42. Stander A, Joubert F, Joubert A. Docking, synthesis, and in vitro evaluation of antimitotic estrone analogs. Chem Biol Drug Des. 2011;77:173-81 pubmed publisher
  43. Innocenti A, Gulcin I, Scozzafava A, Supuran C. Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010;20:5050-3 pubmed publisher
    ..These data may lead to drug design campaigns of effective CAIs possessing a diverse inhibition mechanism compared to sulfonamide/sulfamate inhibitors, based on such less investigated scaffolds. ..
  44. Iannaccone A, Fung K, Eyestone M, Stone E. Treatment of adult-onset acute macular retinoschisis in enhanced s-cone syndrome with oral acetazolamide. Am J Ophthalmol. 2009;147:307-312.e2 pubmed publisher
  45. Cianchi F, Vinci M, Supuran C, Peruzzi B, De Giuli P, Fasolis G, et al. Selective inhibition of carbonic anhydrase IX decreases cell proliferation and induces ceramide-mediated apoptosis in human cancer cells. J Pharmacol Exp Ther. 2010;334:710-9 pubmed publisher
    ..The ability of CA inhibitors to decrease pH(i) might trigger cell apoptosis through mediation of ceramide synthesis. Activation of this apoptotic cascade probably is mediated by inhibition of the CA IX isoform. ..
  46. Faisy C, Mokline A, Sanchez O, Tadie J, Fagon J. Effectiveness of acetazolamide for reversal of metabolic alkalosis in weaning COPD patients from mechanical ventilation. Intensive Care Med. 2010;36:859-63 pubmed publisher
    ..To evaluate the effects of a single daily dose of acetazolamide (ACET) on metabolic alkalosis and respiratory parameters in weaning chronic obstructive pulmonary disease (COPD) patients from invasive mechanical ventilation...
  47. Nishimori I, Minakuchi T, Vullo D, Scozzafava A, Innocenti A, Supuran C. Carbonic anhydrase inhibitors. Cloning, characterization, and inhibition studies of a new beta-carbonic anhydrase from Mycobacterium tuberculosis. J Med Chem. 2009;52:3116-20 pubmed publisher
  48. Höhne C, Pickerodt P, Francis R, Boemke W, Swenson E. Pulmonary vasodilation by acetazolamide during hypoxia is unrelated to carbonic anhydrase inhibition. Am J Physiol Lung Cell Mol Physiol. 2007;292:L178-84 pubmed
    ..is dependent on carbonic anhydrase inhibition by testing other potent heterocyclic sulfonamide carbonic anhydrase inhibitors. Six conscious dogs were studied in five protocols: 1) controls, 2) low-dose intravenous acetazolamide ..
  49. Innocenti A, Hall R, Schlicker C, Scozzafava A, Steegborn C, Muhlschlegel F, et al. Carbonic anhydrase inhibitors. Inhibition and homology modeling studies of the fungal beta-carbonic anhydrase from Candida albicans with sulfonamides. Bioorg Med Chem. 2009;17:4503-9 pubmed publisher
    ..Such compounds may be useful for the design of antifungal agents possessing a new mechanism of action. ..
  50. Tricarico D, Lovaglio S, Mele A, Rotondo G, Mancinelli E, Meola G, et al. Acetazolamide prevents vacuolar myopathy in skeletal muscle of K(+) -depleted rats. Br J Pharmacol. 2008;154:183-90 pubmed publisher
    ..Acetazolamide prevents vacuolar myopathy in K(+)-depleted rats. This effect was associated with inhibition of lactate transport, rather than inhibition of CA. ..