Carbonic anhydrase inhibitors in the treatment and prophylaxis of obesity

Abstract

There are currently very few pharmacological approaches for the treatment of obesity and most of them are unsatisfactory. Furthermore, this disease is widespread in both the developed and developing world and the number of people affected is increasing rapidly. Thus, effective and new approaches are needed for the development of antiobesity agents possessing different mechanisms of action. Solvay Pharmaceuticals recently discovered a revolutionary new approach for the treatment and prophylaxis of obesity, based on the inhibition of carbonic anhydrases (CAs), enzymes involved in several steps of de novo lipogenesis, both in the mitochondria and the cytosol of cells. Topiramate, an antiepileptic drug showing strong CA inhibitory properties, has been used as an example, as clinical data has shown that this compound induces weight loss, as a side effect, in obese patients. It has recently been proven that topiramate is a very potent in vitro inhibitor of several CA isozymes (including CA II and CA V) and that it also inhibits lipogenesis in adipocytes, similar to other sulfonamide CA inhibitors previously investigated. Combining these in vitro data with the clinical observations, the Solvay Pharmaceuticals group logically claimed the two processes to be connected. This is the beginning of a very new and promising approach for the treatment of obesity, with the hope that new compounds displaying this property will soon be developed and available for clinical use.