Applications of carbonic anhydrases inhibitors in renal and central nervous system diseases

Abstract

ABSTRACTIntroduction: There are tissues and organs, among which kidneys and the central nervous system (CNS), rich in various isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Their role is to regulate pH, to provide bicarbonate or H+ ions for electrolyte secretion and possibly a metabolic one. Considering these two systems, CA inhibitors are clinically used mainly as diuretics and antiepileptics, but novel applications in the management of drug-induced renal injury, sleep apnea, migraine, lowering intracranial pressure, cognitive impairment, neuropathic pain, and cerebral ischemia have emerged.Areas covered: The various classes of clinically used/investigational CA inhibitors and their applications in the management of renal and CNS – connected diseases is reviewed. A patent and literature review covering the period 2013–2018 is presented.Expert opinion: Both kidneys and CNS are rich in many CA isoforms (CAIs), present also in high amounts. Their inhibition and activation has pharmacological applications, already exploited for diuretic and antiepileptic drugs for decades. New applications were demonstrated in the last years for the CAIs in the management of idiopathic intracranial hypertension, cerebral ischemia, neuropathic pain, avoiding the disruption of blood-brain barrier, and prevention/treatment of migraine, and for the activators for cognition enhancement and the possible treatment of posttraumatic shock and phobias.