title: Benzolamide is not a membrane-impermeant carbonic anhydrase inhibitor.
abstract: Benzolamide, an orphan drug belonging to the pharmacological class of sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) is widely used in many physiological and pharmacological studies, together with the clinically employed classical drugs, acetazolamide, methazolamide, ethoxzolamide or dichlorophenamide, it being frequently stated that benzolamide is a membrane-impermeant inhibitor. We prove here that this is false: in fact benzolamide is rather similar to acetazolamide from the point of view of penetrability through blood red cell membranes. Unlike these neutral drugs, the cationic, positively-charged CAIs incorporating either tetraalkyl ammonium or pyridinium moieties, due to their salt-like character are indeed membrane-impermeant, being the only type of low molecular weight compound possessing such properties. Selective inhibition of membrane-associated CA isozymes is relevant indeed in many physiological studies and also pharmacologically, since the tumor-associated isozymes (CA IX and XII) are both membrane-bound.
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy. claudiu.supuran@unifi.it
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
mesh_terms: D001574:Benzolamide / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000378:metabolism; D002463:Cell Membrane Permeability; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D002256:Carbonic Anhydrases; D001574:Benzolamide