The potential therapeutic use of phosphodiesterase 10 inhibitors

The discovery of the enzyme phosphodiesterase 10A (PDE10A) was reported simultaneously in 1999 by three independent groups. PDE10A has been shown by localisation studies to have the most restricted distribution of all the 11 known PDE families, with the PDE10A mRNA highly expressed only in the brain and testes. In the brain, mRNA and protein are highly enriched in the striatum and, together with increased pharmacological characterisation, this unique distribution of PDE10A in the brain indicates a potential use of PDE10A inhibitors for treating neurological and psychiatric disorders, in particular, psychotic disorders like schizophrenia. However, PDE10A inhibitors have also been claimed to be useful as treatment for cancer, diabetes and especially obesity. Two years after the reported discovery of PDE10A, Bayer filed the first patent application claiming PDE10A inhibitors, followed shortly thereafter by Pfizer. Since then, a number of scientific publications and filed patents testify to an increasing phar...