Drug interactions of carbonic anhydrase inhibitors and activators

Carbonic anhydrases (CAs, EC 4.2.1.1) have been established drug targets for decades, with their inhibitors and activators possessing relevant pharmacological activity and applications in various fields. At least 11 sulfonamides/sulfamates are clinically used as diuretics, antiglaucoma, antiepileptic, or antiobesity agents and one derivative, SLC-0111, is in clinical trials as antitumor/antimetastatic agent. The activators were less investigated with no clinically used agent.

Drug interactions between CA inhibitors/activators and various other agents are reviewed in publications from the period March 2020 - January 2024.

Drug interactions involving these agents revealed several interesting findings. Acetazolamide plus loop diuretics is highy effective in acute decompensated heart failure, whereas ocular diseases such as X-linked retinoschisis and macular edema were treated by acetazolamide plus bevacizumab or topical NSAIDs. Potent anti-infective effects of acetazolamide and other CAIs, alone or in combination with other agents were demonstrated for the management of Neisseria gonorrhoea, vancomycin resistant enterococci, Acanthamoeba castellanii, Trichinella spiralis, and Cryptococcus neoformans infections. Topiramate, in combination with phentermine is incresingly used for the management of obesity, whereas zonisamide plus levodopa is highly effective for Parkinson's disease. Acetazolamide, methazolamide, ethoxzolamide, and SLC-0111 showed synergistic antitumor/antimetastatic action in combination with many other antitumor drugs.