cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...

that in humans is encoded by the ''PDE10A''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ...

. Various cellular responses are regulated by the second messengers cAMP and cGMP.

Phosphodiesterase A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, ''phosphodiesterase'' refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many oth ...

s, such as PDE10A, eliminate cAMP- and cGMP-mediated intracellular signaling by hydrolyzing the cyclic nucleotide to the corresponding nucleoside 5-prime monophosphate.

Inhibitors

Malamas's PDE10A inhibitor number 96 (2011) in tube model

* Compound 96: IC₅₀ = 700 pM, high selectivity against all other members of the PDE family *

Papaverine Papaverine (Latin ''papaver'', "poppy") is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasms and vasospasms (especially those involving the intestines, heart, or brain), occasionally in the treatment of erec ...

* PF-2545920 * TAK-063: IC₅₀ = 300 pM * AMG 579

Research

Preliminary evidence indicates a possible link between PDE10A expression and obesity in mice and humans.

Inhibitors

Research

References

Further reading