TAK-063

TAK-063 (Balipodect) is a highly potent, selective, orally active PDE10A inhibitor with IC50 of 0.3 nM, displays >15,000-fold selectivity over other PDE subtypes; increases cAMP and cGMP levels in the rodent striatum and upregulates phosphorylation levels of key substrates of cAMP- and cGMP-dependent protein kinases, strongly suppresses MK-801-induced hyperlocomotion in rodents (0.3 and 1 mg/kg p.o), improves cognitive functions associated with schizophrenia in rodent models, Schizophrenia Phase 2 Discontinued (In Vivo) :Balipodect (TAK-063) has excellent selectivity (>15000-fold selectivity over other PDEs), and favorable pharmacokinetics, including high brain penetration, in mice. Oral administration of Balipodect (TAK-063) to mice elevated striatal 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) levels at 0.3 mg/kg and showed potent suppression of phencyclidine (PCP) -induced hyperlocomotion at a minimum effective dose (MED) of 0.3 mg/kg.Balipodect (TAK-063) at 0.3 and 1 mg/kg, p.o., increased cAMP and cGMP levels in the rodent striatum and upregulated phosphorylation levels of key substrates of cAMP-dependent and cGMP-dependent protein kinases. Balipodect (TAK-063) at 0.3 and 1 mg/kg, p.o., strongly suppressed MK-801-induced hyperlocomotion that is often used as a predictive model for antipsychotic-like activity in rodents. Balipodect (TAK-063) did not affect plasma prolactin or glucose levels at doses up to 3 mg/kg, p.o. Balipodect (TAK-063) at 3 mg/kg, p.o., elicited a weak cataleptic response compared with haloperidol and olanzapine.