The potential therapeutic use of phosphodiesterase 10 inhibitors

Abstract

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 pharmaceutical interest in this target. This article highlights and reviews research advances published in the patent literature between the first patent publication in June 2002 and November 2006. The article is supplemented with selected publications from the scientific literature, emphasising the possible involvement of PDE10A inhibitors in the treatment of schizophrenia and referring to studies aimed at understanding their mechanism and pathophysiology.

Keywords::

• MP-10
• PDE10A
• phosphodiesterase 10A inhibitor
• psychosis
• schizophrenia

Acknowledgements

We would like to thank M Langgård and J Nielsen for helpful discussions during the preparation of this manuscript.

Notes