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_10A subtype. The PDE_10A enzyme is expressed primarily in the brain, mostly in the

striatum The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamate ...

, nucleus accumbens and

olfactory tubercle The olfactory tubercle (OT), also known as the tuberculum olfactorium, is a multi-sensory processing center that is contained within the olfactory cortex and ventral striatum and plays a role in reward cognition. The OT has also been shown to ...

, and is thought to be particularly important in regulating the activity of

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

-sensitive medium spiny neurons in the striatum which are known to be targets of conventional antipsychotic drugs. Older PDE_10A inhibitors such as papaverine have been shown to produce antipsychotic effects in animal models, and more potent and selective PDE_10A inhibitors are a current area of research for novel antipsychotic drugs which act through a different pathway to conventional dopamine or 5-HT_2A antagonist drugs and may have a more favourable side effects profile. Mardepodect is currently one of the furthest advanced PDE_10A inhibitors in development and has progressed through to Phase II

clinical trials Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

in humans. In 2017, development of mardepodect for the treatment of schizophrenia and Huntington's disease was discontinued.

References

{{Phosphodiesterase inhibitors Abandoned drugs Pfizer brands Phenol ethers Phosphodiesterase inhibitors Pyrazoles 4-Pyridyl compounds Quinolines