Carbonic anhydrase inhibitors as anticonvulsant agents.
Seizures are one of the most common neurological disorders in clinical medicine. Triggering mechanisms by which seizures form remain unclear, but are related to a rapid change in ionic composition, including an increase of intracellular potassium concentration and pH shifts within the brain. pH buffering of extra- and intracellular spaces is mainly carried out by the CO(2)/ HCO(3)(-) buffer, the equilibration of the two species being assured by the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). Some carbonic anhydrase inhibitors (CAIs) are used as anticonvulsants in the treatment of epilepsy. In this review, we will describe the link between CA and seizures on the basis of several putative mechanisms. Several CA isozymes have been pointed out for their contribution to epileptiform activity. An overview of the CA isozyme expression in the brain and of their specifics roles is also discussed. This article reviews the research achievements published on CA inhibitors, clinically used as anticonvulsant and those under development.
Thiry
Anne
A
Drug Design and Discovery Center, FUNDP, University of Namur, Namur, Belgium. anne.thiry@fundp.ac.be
Dogné
Jean-Michel
JM
Supuran
Claudiu T
CT
Masereel
Bernard
B
D000927:Anticonvulsants; D001923:Brain Chemistry; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use*; D002256:Carbonic Anhydrases / Q000502:physiology; D006801:Humans; D007527:Isoenzymes; D012640:Seizures / Q000188:drug therapy / Q000209:etiology
D000927:Anticonvulsants; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D002256:Carbonic Anhydrases