Characterization of Binding and Inhibitory Properties of TAK-063, a Novel Phosphodiesterase 10A Inhibitor
Fig 5
In vivo occupancy study of TAK-063 using T-773 as a tracer in rats.
In in vitro ARG study using the rat brain sagittal section, [3H]T-773 selectively accumulated in the caudate putamen (CPu; white arrow), globus pallidus (GP; black arrow), nucleus accumbens (NAc; white arrow head), substantia nigra (SN; black arrow head), and striatonigral projection (gray arrow), where PDE10A is highly expressed (A). This accumulation was almost completely blocked by an excess amount of TAK-063 (B). PDE10A occupancy (%) in the striatum was plotted against doses of orally administered TAK-063 in rats with intravenous T-773 injection (C). The cerebellum was used as a reference region. PDE10A occupancy was increased in a dose-dependent manner. Oral administration of 0.88 mg/kg of TAK-063 resulted in 50% PDE10A occupancy as determined by regression analysis.