Mardepodect (developmental code name PF-2545920) is a drug which was developed by Pfizer for the treatment of schizophrenia. It acts as a phosphodiesterase inhibitor selective for the PDE<sub>10A</sub> subtype.
The PDE<sub>10A</sub> enzyme is expressed primarily in the brain, mostly in the striatum, nucleus accumbens and olfactory tubercle, and is thought to be particularly important in regulating the activity of dopamine-sensitive medium spiny neurons in the striatum which are known to be targets of conventional antipsychotic drugs. Older PDE<sub>10A</sub> inhibitors such as papaverine have been shown to produce antipsychotic effects in animal models, and more potent and selective PDE<sub>10A</sub> inhibitors are a current area of research for novel antipsychotic drugs which act through a different pathway to conventional dopamine or 5-HT<sub>2A</sub> antagonist drugs and may have a more favourable side effects profile.
Mardepodect is currently one of the furthest advanced PDE<sub>10A</sub> inhibitors in development and has progressed through to Phase II clinical trials in humans. In 2017, development of mardepodect for the treatment of schizophrenia and Huntington's disease was discontinued.