Translational Development Strategies for TAK-063, a Phosphodiesterase 10A Inhibitor.

ABSTRACT:

Background

TAK-063 is an inhibitor of phosphodiesterase 10A (PDE10A), an enzyme highly expressed in medium spiny neurons of the striatum. PDE10A hydrolyzes both cyclic adenosine monophosphate and cyclic guanosine monophosphate and modulates dopamine signaling downstream of receptor activation in both direct and indirect pathways of the striatum. TAK-063 exhibited antipsychotic-like effects in animal models; however, the translatability of these models to the clinical manifestations of schizophrenia and the meaningfulness for new targets such as PDE10A has not been established.

Methods

The TAK-063 phase 1 program included a comprehensive translational development strategy with the main objective of determining whether the antipsychotic-like pharmacodynamic effects seen in non

SUBMITTER: Macek TA 

PROVIDER: S-EPMC7689203 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature