UNASSIGNED: @entity68713 ( @entity68713 ) is a @entity268 / @entity6708 phosphodiesterase highly expressed in medium spiny neurons (MSNs) in the striatum. We evaluated the in vivo pharmacological profile of a potent and selective @entity68713 inhibitor TAK-063 [1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)-pyridazin-4(1H)-one]. TAK-063 at 0.3 and 1 mg/kg, p.o., increased @entity268 and @entity6708 levels in the rodent striatum and upregulated phosphorylation levels of key substrates of @entity268 -dependent and @entity6708 -dependent protein kinases. TAK-063 at 0.3 and 1 mg/kg, p.o., strongly suppressed @entity3390 -induced hyperlocomotion that is often used as a predictive model for antipsychotic-like activity in rodents. Upregulation of striatal @entity268 / @entity6708 levels and the antipsychotic-like effect of TAK-063 were not attenuated after 15 days of pretreatment with TAK-063 in @entity19 . The potential side effect profile of TAK-063 was assessed in @entity35 using the clinical antipsychotics @entity1767 , @entity1037 , and @entity1770 as controls. TAK-063 did not affect plasma prolactin or @entity413 levels at doses up to 3 mg/kg, p.o. TAK-063 at 3 mg/kg, p.o., elicited a weak cataleptic response compared with @entity1767 and @entity1037 . Evaluation of pathway-specific markers (substance P mRNA for the direct pathway and @entity10971 mRNA for the indirect pathway) revealed that TAK-063 activated both the direct and indirect pathways of MSNs. These findings suggest that TAK-063 represents a promising drug for the treatment of @entity161 with the potential for a superior safety and tolerability profiles.

In Vivo Pharmacological Characterization of TAK-063, a Potent and Selective XXXX Inhibitor with Antipsychotic-Like Activity in Rodents.

@entity68713 :: ('63885(Tax:10116)', 'Gene') :: ['Phosphodiesterase 10A', 'PDE10A'] @entity6708 :: ('CHEBI:16356', 'Chemical') :: ['cGMP'] @entity268 :: ('CHEBI:17489', 'Chemical') :: ['cAMP'] @entity1037 :: ('MESH:C076029', 'Chemical') :: ['olanzapine'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity10971 :: ('29237(Tax:10116)', 'Gene') :: ['enkephalin'] @entity161 :: ('MESH:D012559', 'Disease') :: ['schizophrenia'] @entity1767 :: ('MESH:D006220', 'Chemical') :: ['haloperidol'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity3390 :: ('MESH:D016291', 'Chemical') :: ['MK-801'] @entity1770 :: ('MESH:C094645', 'Chemical') :: ['aripiprazole'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']
@entity68713 :: (63885(Tax:10116),Gene) :: ['Phosphodiesterase 10A']
