Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity.
BACKGROUND
Obesity is a widespread disease in both the developed and developing world. Few pharmacological approaches for its treatment exist at this time.


OBJECTIVE
This review summarises the currently approved obesity therapies and describes a possible new approach for the treatment and prophylaxis of this disease, based on the inhibition of carbonic anhydrases (CAs, EC 4.2.1.1), enzymes involved in several steps of de novo lipogenesis, both in the mitochondria and the cytosol of cells.


METHODS
Topiramate and zonisamide, two antiepileptic drugs showing strong CA inhibitory properties, have been reported as an example of this approach, as clinical data have shown that these compounds induce persistent weight loss in obese patients.


CONCLUSIONS
The use of topiramate and zonisamide as lead molecules for the design of CA inhibitors targeting isozymes involved in lipogenesis could represent the beginning of a very promising new approach for the treatment of obesity.
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
Claudiu T
CT
Supuran
Anna
A
Di Fiore
Giuseppina
G
De Simone
D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000517:prevention & control; D000077236:Topiramate; D000078305:Zonisamide
D019440:Anti-Obesity Agents; D002257:Carbonic Anhydrase Inhibitors; D007555:Isoxazoles; D000077236:Topiramate; D005632:Fructose; D000078305:Zonisamide