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TAK-063, a novel PDE10A inhibitor with balanced activation of direct and indirect pathways, provides a unique opportunity for the treatment of schizophrenia.
Suzuki K, Kimura H. Suzuki K, et al. CNS Neurosci Ther. 2018 Jul;24(7):604-614. doi: 10.1111/cns.12798. Epub 2018 Jan 9. CNS Neurosci Ther. 2018. PMID: 29318783 Free PMC article. Review.
TAK-063, with a faster off-rate property, could provide a unique opportunity as a novel therapeutic approach to treatment of psychosis and cognitive deficits in schizophrenia. TAK-063 also has a therapeutic potential in other basal ganglia disorders... …
TAK-063, with a faster off-rate property, could provide a unique opportunity as a novel therapeutic approach to treatment of p …
Translational Development Strategies for TAK-063, a Phosphodiesterase 10A Inhibitor.
Macek TA, Suzuki K, Asin K, Kimura H. Macek TA, et al. Int J Neuropsychopharmacol. 2020 Nov 26;23(8):524-532. doi: 10.1093/ijnp/pyaa042. Int J Neuropsychopharmacol. 2020. PMID: 32598478 Free PMC article.
BACKGROUND: TAK-063 is an inhibitor of phosphodiesterase 10A (PDE10A), an enzyme highly expressed in medium spiny neurons of the striatum. ...TAK-063 showed favorable pharmacokinetic and safety profiles in humans, and TAK-063 reduced keta …
BACKGROUND: TAK-063 is an inhibitor of phosphodiesterase 10A (PDE10A), an enzyme highly expressed in medium spiny neurons of t …
TAK-063, a phosphodiesterase 10A inhibitor, modulates neuronal activity in various brain regions in phMRI and EEG studies with and without ketamine challenge.
Tomimatsu Y, Cash D, Suzuki M, Suzuki K, Bernanos M, Simmons C, Williams SC, Kimura H. Tomimatsu Y, et al. Neuroscience. 2016 Dec 17;339:180-190. doi: 10.1016/j.neuroscience.2016.10.006. Epub 2016 Oct 8. Neuroscience. 2016. PMID: 27725212
TAK-063 at 0.3mg/kg significantly reduced the ketamine-induced increase in EEG gamma power both in awake and anesthetized rats. TAK-063 at 0.2mg/kg (35% PDE10A occupancy in monkeys) also reduced the ketamine-induced increase in EEG gamma power in awake …
TAK-063 at 0.3mg/kg significantly reduced the ketamine-induced increase in EEG gamma power both in awake and anesthetized rats …
TAK-063, a Novel Phosphodiesterase 10A Inhibitor, Protects from Striatal Neurodegeneration and Ameliorates Behavioral Deficits in the R6/2 Mouse Model of Huntington's Disease.
Harada A, Suzuki K, Kimura H. Harada A, et al. J Pharmacol Exp Ther. 2017 Jan;360(1):75-83. doi: 10.1124/jpet.116.237388. Epub 2016 Nov 3. J Pharmacol Exp Ther. 2017. PMID: 27811172
TAK-063 at 0.5 or 5 mg/kg/day was orally administrated from 4.5-5 to 12 weeks of age, and the effects of TAK-063 were characterized over this period. ...These results suggest that TAK-063 reduces striatal neurodegeneration and ameliorates …
TAK-063 at 0.5 or 5 mg/kg/day was orally administrated from 4.5-5 to 12 weeks of age, and the effects of TAK-063 …
TAK-063, a PDE10A Inhibitor with Balanced Activation of Direct and Indirect Pathways, Provides Potent Antipsychotic-Like Effects in Multiple Paradigms.
Suzuki K, Harada A, Suzuki H, Miyamoto M, Kimura H. Suzuki K, et al. Neuropsychopharmacology. 2016 Aug;41(9):2252-62. doi: 10.1038/npp.2016.20. Epub 2016 Feb 5. Neuropsychopharmacology. 2016. PMID: 26849714 Free PMC article.
TAK-063 and MP-10 activated the indirect pathway to a similar extent; however, MP-10 caused greater activation of the direct pathway than did TAK-063. Interestingly, the off-rate of TAK-063 from PDE10A in rat brain sections was faster tha …
TAK-063 and MP-10 activated the indirect pathway to a similar extent; however, MP-10 caused greater activation of the direct p …
The PDE10A Inhibitor TAK-063 Reverses Sound-Evoked EEG Abnormalities in a Mouse Model of Fragile X Syndrome.
Jonak CR, Sandhu MS, Assad SA, Barbosa JA, Makhija M, Binder DK. Jonak CR, et al. Neurotherapeutics. 2021 Apr;18(2):1175-1187. doi: 10.1007/s13311-021-01005-w. Epub 2021 Feb 16. Neurotherapeutics. 2021. PMID: 33594533 Free PMC article.
We demonstrate significant dose-related amelioration of inter-trial phase coherence (ITPC) to temporally modulated auditory stimuli by TAK-063 in Fmr1 KO mice. Our data suggest that TAK-063 improves cortical auditory stimulus processing in Fmr1 KO mice …
We demonstrate significant dose-related amelioration of inter-trial phase coherence (ITPC) to temporally modulated auditory stimuli by TA …
Pre-clinical Characterization of Absorption, Distribution, Metabolism and Excretion Properties of TAK-063.
Tohyama K, Sudo M, Morohashi A, Kato S, Takahashi J, Tagawa Y. Tohyama K, et al. Basic Clin Pharmacol Toxicol. 2018 Jun;122(6):577-587. doi: 10.1111/bcpt.12964. Epub 2018 Feb 26. Basic Clin Pharmacol Toxicol. 2018. PMID: 29345044 Free article.
TAK-063 is currently being developed to treat schizophrenia. In this study, we investigated the absorption, distribution, metabolism and excretion (ADME) properties of TAK-063 using several paradigms. Following oral administration of TAK-063 …
TAK-063 is currently being developed to treat schizophrenia. In this study, we investigated the absorption, distribution, meta …
The Phosphodiesterase 10A Selective Inhibitor TAK-063 Improves Cognitive Functions Associated with Schizophrenia in Rodent Models.
Shiraishi E, Suzuki K, Harada A, Suzuki N, Kimura H. Shiraishi E, et al. J Pharmacol Exp Ther. 2016 Mar;356(3):587-95. doi: 10.1124/jpet.115.230482. Epub 2015 Dec 16. J Pharmacol Exp Ther. 2016. PMID: 26675680
TAK-063 at 0.1 and 0.3 mg/kg p.o. improved time-dependent memory decay in object recognition in naive rats. TAK-063 at 0.1 and 0.3 mg/kg p.o. increased accuracy rate, and TAK-063 at 0.3 mg/kg p.o. reduced impulsivity in a five-choice seri …
TAK-063 at 0.1 and 0.3 mg/kg p.o. improved time-dependent memory decay in object recognition in naive rats. TAK-063 …
The phosphodiesterase 10A selective inhibitor, TAK-063, induces c-Fos expression in both direct and indirect pathway medium spiny neurons and sub-regions of the medial prefrontal cortex in rats.
Nakatani A, Nakamura S, Kimura H. Nakatani A, et al. Neurosci Res. 2017 Dec;125:29-36. doi: 10.1016/j.neures.2017.06.007. Epub 2017 Jul 4. Neurosci Res. 2017. PMID: 28687229
TAK-063 at 0.3 and 3mg/kg induced a dose-dependent increase in the number of c-Fos immunoreactive cells in the striatal complex. Furthermore, TAK-063 increased the number of MSNs expressing c-fos mRNA in both the D(1) receptor-expressing direct pathway …
TAK-063 at 0.3 and 3mg/kg induced a dose-dependent increase in the number of c-Fos immunoreactive cells in the striatal comple …
In vivo pharmacological characterization of TAK-063, a potent and selective phosphodiesterase 10A inhibitor with antipsychotic-like activity in rodents.
Suzuki K, Harada A, Shiraishi E, Kimura H. Suzuki K, et al. J Pharmacol Exp Ther. 2015 Mar;352(3):471-9. doi: 10.1124/jpet.114.218552. Epub 2014 Dec 18. J Pharmacol Exp Ther. 2015. PMID: 25525190
Upregulation of striatal cAMP/cGMP levels and the antipsychotic-like effect of TAK-063 were not attenuated after 15 days of pretreatment with TAK-063 in mice. ...TAK-063 did not affect plasma prolactin or glucose levels at doses up to 3 m …
Upregulation of striatal cAMP/cGMP levels and the antipsychotic-like effect of TAK-063 were not attenuated after 15 days of pr …
25 results