Mardepodect
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 subtype. The PDE 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 inhibitors such as papaverine have been shown to produce antipsychotic effects in animal models, and more potent and selective PDE  inhibitors are a current area of research for novel antipsychotic drugs which act through a different pathway to conventional dopamine or 5-HT antagonist drugs and may have a more favourable side effects profile. Mardepodect is currently one of the furthest advanced PDE 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.