title: Carbonic anhydrase inhibition for the management of cerebral ischemia: in vivo evaluation of sulfonamide and coumarin inhibitors.
abstract: Ischemia of brain areas is a global health problem, causing death or long-term disability. Current pharmacological options have limited impact on ischemic damages. Recently, a relationship between hypoxia and carbonic anhydrase (CA) over-expression has been highlighted suggesting CA inhibition as a possible target. This study aimed to evaluate the pharmacological profile of sulfonamide and coumarin CA inhibitors in rats underwent permanent middle cerebral artery occlusion (pMCAO). The neurological score of pMCAO rats was dramatically reduced 24 h after occlusion. Repeated subcutaneous injections of the CA inhibitors 4 and 7 (1 mg kg(-1)) were able to increase the neurological score by 40%. Compound 7 showed the tendency to reduce the volume of hemisphere infarction. The standard CA inhibitor acetazolamide was ineffective. The properties of novel CA inhibitors to improve neurological functionalities after cerebral ischemic insult are shown. The CA involvement in cerebral hypoxic phenomena deserves deeper investigations.
authors.affiliation: a Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino - NEUROFARBA - Sezione di Farmacologia e Tossicologia, Università degli Studi di Firenze , Florence , Italy .
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.affiliation: a Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino - NEUROFARBA - Sezione di Farmacologia e Tossicologia, Università degli Studi di Firenze , Florence , Italy .
authors.forename: Laura
authors.initials: L
authors.lastname: Micheli
authors.affiliation: b Dipartimento Di Chimica, Laboratorio Di Chimica Bioinorganica, Università Degli Studi Di Firenze , Sesto Fiorentino , Florence , Italy .
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carta
authors.affiliation: c Dipartimento di Medicina Clinica e Sperimentale - DMSC - Università degli Studi di Firenze , Florence , Italy , and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cozzi
authors.affiliation: a Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino - NEUROFARBA - Sezione di Farmacologia e Tossicologia, Università degli Studi di Firenze , Florence , Italy .
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.affiliation: b Dipartimento Di Chimica, Laboratorio Di Chimica Bioinorganica, Università Degli Studi Di Firenze , Sesto Fiorentino , Florence , Italy .|d Dipartimento Neurofarba, Sezione Di Scienze Farmaceutiche, Polo Scientifico, Università Degli Studi Di Firenze , Sesto Fiorentino , Florence , Italy.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D003374:Coumarins; D013449:Sulfonamides; C030123:coumarin; D002256:Carbonic Anhydrases
keywords: Acetazolamide; carbonic anhydrase; coumarin; neurological score; pMCAO; sulfonamide