Abstract
Phosphodiesterase 10A (PDE10A) is a double substrate enzyme that hydrolyzes second messenger molecules such as cyclic-3’,5’-adenosine monophosphate (cAMP) and cyclic-3’,5’-guanosine monophosphate (cGMP). Through this process, PDE10A controls intracellular signaling pathways in the mammalian brain and peripheral tissues. Pharmacological, biochemical, and anatomical data suggest that disorders in the second messenger system mediated by PDE10A may contribute to impairments in the central nervous system (CNS) function, including cognitive deficits as well as disturbances of behavior, emotion processing, and movement. This review provides a detailed description of PDE10A and the recent advances in the design of selective PDE10A inhibitors. The results of preclinical studies regarding the potential utility of PDE10A inhibitors for the treatment of CNS-related disorders, such as schizophrenia as well as Huntington’s and Parkinson’s diseases are also summarized.
Keywords: PDE10A inhibitors, second messenger system, SAR study, CNS disorders, papaverine-related compounds, isoquinoline.
Graphical Abstract
[1]
Brescia M, Zaccolo M. Modulation of Compartmentalised Cyclic Nucleotide Signalling via Local Inhibition of Phosphodiesterase Activity. Int J Mol Sci 2016; 17(10): E1672.
[2]
Jankowska A, Świerczek A, Chłoń-Rzepa G, Pawłowski M, Wyska E. PDE7-Selective and Dual Inhibitors: Advances in Chemical and Biological Research. Curr Med Chem 2017; 24(7): 673-700.
[3]
Keravis T, Lugnier C. Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments. Br J Pharmacol 2012; 165(5): 1288-305.
[4]
Lakics V, Karran EH, Boess FG. Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues. Neuropharmacol 2010; 59(6): 367-74.
[5]
Xu Y, Zhang HT, O’Donnell JM. Phosphodiesterases in the central nervous system: implications in mood and cognitive disorders. Handb Exp Pharmacol 2011; 204: 447-85.
[6]
Wang ZZ, Zhang Y, Zhang HT, Li YF. Phosphodiesterase: an interface connecting cognitive deficits to neuropsychiatric and neurodegenerative diseases. Curr Pharm Des 2015; 21(3): 303-16.
[7]
Cheng YF, Wang C, Lin HB, et al. Inhibition of phosphodiesterase-4 reverses memory deficits produced by Aβ25-35 or Aβ1-40 peptide in rats. Psychopharmacol (Berl) 2010; 212(2): 181-91.
[8]
Miao Y, He T, Zhu Y, Li W, Wang B, Zhong Y. Activation of Hippocampal CREB by Rolipram Partially Recovers Balance Between TNF-α and IL-10 Levels and Improves Cognitive Deficits in Diabetic Rats. Cell Mol Neurobiol 2015; 35(8): 1157-64.
[9]
Titus DJ, Sakurai A, Kang Y, et al. Phosphodiesterase inhibition rescues chronic cognitive deficits induced by traumatic brain injury. J Neurosci 2013; 33(12): 5216-26.
[10]
Valdés-Moreno MI, Alcántara-Alonso V, Estrada-Camarena E, et al. Phosphodiesterase-7 inhibition affects accumbal and hypothalamic thyrotropin-releasing hormone expression, feeding and anxiety behavior of rats. Behav Brain Res 2017; 319: 165-73.
[11]
Siuciak JA, Chapin DS, McCarthy SA, Martin AN. Antipsychotic profile of rolipram: efficacy in rats and reduced sensitivity in mice deficient in the phosphodiesterase-4B (PDE4B) enzyme. Psychopharmacol (Berl) 2007; 192(3): 415-24.
[12]
Li YF, Huang Y, Amsdell SL, Xiao L, O’Donnell JM, Zhang HT. Antidepressant- and anxiolytic-like effects of the phosphodiesterase-4 inhibitor rolipram on behavior depend on cyclic AMP response element binding protein-mediated neurogenesis in the hippocampus. NeuroPsychopharmacol 2009; 34(11): 2404-19.
[13]
Zhang MZ, Zhou ZZ, Yuan X, et al. Chlorbipram: A novel PDE4 inhibitor with improved safety as a potential antidepressant and cognitive enhancer. Eur J Pharmacol 2013; 721(1-3): 56-63.
[14]
Redondo M, Brea J, Perez DI, et al. Effect of phosphodiesterase 7 (PDE7) inhibitors in experimental autoimmune encephalomyelitis mice. Discovery of a new chemically diverse family of compounds. J Med Chem 2012; 55(7): 3274-84.
[15]
Kadoshima-Yamaoka K, Murakawa M, Goto M, et al. ASB16165, a novel inhibitor for phosphodiesterase 7A (PDE7A), suppresses IL-12-induced IFN-γ production by mouse activated T lymphocytes. Immunol Lett 2009; 122(2): 193-7.
[16]
Kadoshima-Yamaoka K, Murakawa M, Goto M, et al. Effect of phosphodiesterase 7 inhibitor ASB16165 on development and function of cytotoxic T lymphocyte. Int Immunopharmacol 2009; 9(1): 97-102.
[17]
Paterniti I, Mazzon E, Gil C, et al. PDE 7 inhibitors: New potential drugs for the therapy of spinal cord injury. PLoS One 2011; 6(1): e15937.
[18]
Redondo M, Zarruk JG, Ceballos P, et al. Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental stroke model. Eur J Med Chem 2012; 47(1): 175-85.
[19]
Goto M, Murakawa M, Kadoshima-Yamaoka K, et al. Phosphodiesterase 7A inhibitor ASB16165 suppresses proliferation and cytokine production of NKT cells. Cell Immunol 2009; 258(2): 147-51.
[20]
Perez-Gonzalez R, Pascual C, Antequera D, et al. Phosphodiesterase 7 inhibitor reduced cognitive impairment and pathological hallmarks in a mouse model of Alzheimer’s disease. Neurobiol Aging 2013; 34(9): 2133-45.
[21]
Vollert S, Kaessner N, Heuser A, et al. The glucose-lowering effects of the PDE4 inhibitors roflumilast and roflumilast-N-oxide in db/db mice. Diabetologia 2012; 55(10): 2779-88.
[23]
Kandel ER. The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB. Mol Brain 2012; 5: 14.
[24]
Yu XW, Oh MM, Disterhoft JF. CREB, cellular excitability, and cognition: Implications for aging. Behav Brain Res 2017; 322: 206-11.
[25]
Kleppisch T, Feil R. cGMP signalling in the mammalian brain: role in synaptic plasticity and behaviour. Handb Exp Pharmacol 2009; 191: 549-79.
[26]
Reierson GW, Guo S, Mastronardi C, Licinio J, Wong ML. cGMP signaling, phosphodiesterases and major depressive disorder. Curr Neuropharmacol 2011; 9(4): 715-27.
[27]
Raker VK, Becker C, Steinbrink K. The cAMP Pathway as Therapeutic Target in Autoimmune and Inflammatory Diseases. Front Immunol 2016; 7: 123.
[28]
Rapôso C, Luna RL, Nunes AK, Thomé R, Peixoto CA. Role of iNOS-NO-cGMP signaling in modulation of inflammatory and myelination processes. Brain Res Bull 2014; 104: 60-73.
[29]
Lee D. Global and local missions of cAMP signaling in neural plasticity, learning, and memory. Front Pharmacol 2015; 6: 161.
[30]
Boess FG, Hendrix M, van der Staay FJ, et al. Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance. Neuropharmacol 2004; 47(7): 1081-92.
[31]
Silveira MS, Linden LR. Neuroprotection by cAMP: Another brick in the wall. Adv Exp Med Biol 2006; 557: 164-76.
[32]
Mastrodimou N, Kiagiadaki F, Thermos K. The role of nitric oxide and cGMP in somatostatin’s protection against retinal ischemia. Invest Ophthalmol Vis Sci 2008; 49(1): 342-9.
[33]
Johansson EM, Reyes-Irisarri E, Mengod G. Comparison of cAMP-specific phosphodiesterase mRNAs distribution in mouse and rat brain. Neurosci Lett 2012; 525(1): 1-6.
[35]
Soderling SH, Bayuga SJ, Beavo JA. Isolation and Characterization of a Dual-Substrate Phosphodiesterase Gene Family: PDE10A. Pharmacology 1999; 96: 7071-6.
[36]
Loughney K, Snyder PB, Uher L, Rosman GJ, Ferguson K, Florio VA. Isolation and characterization of PDE10A, a novel human 3′, 5′-cyclic nucleotide phosphodiesterase. Gene 1999; 234(1): 109-17.
[37]
Fujishige K, Kotera J, Omori K. Striatum- and testis-specific phosphodiesterase PDE10A: Isolation and characterization of a rat PDE10A. Eur J Biochem 1999; 266(3): 1118-27.
[38]
Kotera J, Fujishige K, Yuasa K, Omori K. Characterization and phosphorylation of PDE10A2, a novel alternative splice variant of human phosphodiesterase that hydrolyzes cAMP and cGMP. Biochem Biophys Res Commun 1999; 261(26): 551-7.
[39]
MacMullen CM, Fallahi M, Davis RL. Novel PDE10A transcript diversity in the human striatum: Insights into gene complexity, conservation and regulation. Gene 2017; 606: 17-24.
[40]
Charych EI, Jiang LX, Lo F, Sullivan K, Brandon NJ. Interplay of palmitoylation and phosphorylation in the trafficking and localization of phosphodiesterase 10A: implications for the treatment of schizophrenia. J Neurosci 2010; 30(27): 9027-37.
[41]
Handa N, Mizohata E, Kishishita S, et al. Crystal structure of the GAF-B domain from human phosphodiesterase 10A complexed with its ligand, cAMP. J Biol Chem 2008; 283(28): 19657-64.
[42]
Russwurm C, Koesling D, Russwurm M. Phosphodiesterase 10A is tethered to a synaptic signaling complex in striatum. J Biol Chem 2015; 290(19): 11936-47.
[43]
Seeger TF, Bartlett B, Coskran TM, et al. Immunohistochemical localization of PDE10A in the rat brain. Brain Res 2003; 985(2): 113-26.
[44]
Bodén R, Persson J, Wall A, et al. Striatal phosphodiesterase 10A and medial prefrontal cortical thickness in patients with schizophrenia: a PET and MRI study. Transl Psychiatry 2017; 7(3): e1050.
[45]
Kotera J, Sasaki T, Kobayashi T, Fujishige K, Yamashita Y, Omori K. Subcellular Localization of Cyclic Nucleotide Phosphodiesterase Type 10A Variants, and Alteration of the Localization by cAMP-dependent Protein Kinase-dependent Phosphorylation. J Biol Chem 2004; 279(6): 4366-75.
[46]
MacMullen CM, Vick K, Pacifico R, Fallahi-Sichani M, Davis RL. Novel, primate-specific PDE10A isoform highlights gene expression complexity in human striatum with implications on the molecular pathology of bipolar disorder. Transl Psychiatry 2016; 6(2): e742.
[47]
Ho GD, Michael Seganish W, Bercovici A, et al. The SAR development of dihydroimidazoisoquinoline derivatives as phosphodiesterase 10A inhibitors for the treatment of schizophrenia. Bioorganic Med Chem Lett 2012; 22(7): 2585-9.
[48]
Zhang Z, Lu X, Xu J, Rothfuss J, Mach RH, Tu Z. Synthesis and in vitro evaluation of new analogues as inhibitors for phosphodiesterase 10A. Eur J Med Chem 2011; 46(9): 3986-95.
[49]
Rzasa RM, Frohn MJ, Andrews KL, et al. Synthesis and preliminary biological evaluation of potent and selective 2-(3-alkoxy-1-azetidinyl)quinolines as novel PDE10A inhibitors with improved solubility. Bioorganic Med Chem 2014; 22(23): 6570-85.
[50]
Hamaguchi W, Masuda N, Miyamoto S, et al. Synthesis, SAR study, and biological evaluation of novel quinoline derivatives as phosphodiesterase 10A inhibitors with reduced CYP3A4 inhibition. Bioorganic Med Chem 2015; 23(2): 297-313.
[51]
Verhoest PR, Chapin DS, Corman M, et al. Discovery of a novel class of phosphodiesterase 10A inhibitors and identification of clinical candidate 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the treatment of schizophrenia. J Med Chem 2009; 52(16): 5188-96.
[52]
Hu E, Kunz RK, Rumfelt S, et al. Use of structure based design to increase selectivity of pyridyl-cinnoline phosphodiesterase 10A (PDE10A) inhibitors against phosphodiesterase 3 (PDE3). Bioorganic Med Chem Lett 2012; 22(22): 6938-42.
[53]
Hu E, Kunz RK, Rumfelt S, et al. Discovery of potent, selective, and metabolically stable 4-(pyridin-3-yl)cinnolines as novel phosphodiesterase 10A (PDE10A) inhibitors. Bioorganic Med Chem Lett 2012; 22(6): 2262-5.
[54]
Wagner S, Scheunemann M, Dipper K, et al. Development of highly potent phosphodiesterase 10A (PDE10A) inhibitors: Synthesis and in vitro evaluation of 1,8-dipyridinyl- and 1-pyridinyl-substituted imidazo[1,5-a]quinoxalines. Eur J Med Chem 2016; 107: 97-108.
[55]
Chappie TA, Humphrey JM, Allen MP, et al. Discovery of a Series of 6,7-Dimethoxy-4-pyrrolidylquinazoline PDE10A Inhibitors. J Med Chem 2007; 50(2): 182-5.
[56]
Dore A, Asproni B, Scampuddu A, et al. Synthesis and SAR study of novel tricyclic pyrazoles as potent phosphodiesterase 10A inhibitors. Eur J Med Chem 2014; 84: 181-93.
[57]
Raheem IT, Breslin MJ, Fandozzi C, et al. Discovery of tetrahydropyridopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophrenia. Bioorganic Med Chem Lett 2012; 22(18): 5903-8.
[58]
Raheem IT, Schreier JD, Fuerst J, et al. Discovery of pyrazolopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophrenia. Bioorganic Med Chem Lett 2016; 26(1): 126-32.
[59]
Yoshikawa M, Kamisaki H, Kunitomo J, et al. Design and synthesis of a novel 2-oxindole scaffold as a highly potent and brain-penetrant phosphodiesterase 10A inhibitor. Bioorganic Med Chem 2015; 23(22): 7138-49.
[60]
Yang SW, Smotryski J, Mcelroy WT, et al. Discovery of orally active pyrazoloquinolines as potent PDE10 inhibitors for the management of schizophrenia. Bioorganic Med Chem Lett 2012; 22(1): 235-9.
[61]
Vlasceanu A, Jessing M, Paul J. BN/CC isosterism in borazaronaphthalenes towards phosphodiesterase 10A (PDE10A) inhibitors. Bioorganic Med Chem 2015; 23(15): 4453-61.
[62]
Gage JL, Onrust R, Johnston D, et al. N-Acylhydrazones as inhibitors of PDE10A. Bioorganic Med Chem Lett 2011; 21(14): 4155-9.
[63]
Cutshall NS, Onrust R, Rohde A, et al. Novel 2-methoxyacylhydrazones as potent, selective PDE10A inhibitors with activity in animal models of schizophrenia. Bioorganic Med Chem Lett 2012; 22(17): 5595-9.
[64]
Grauer SM, Pulito VL, Navarra RL, et al. Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia. J Pharmacol Exp Ther 2009; 331(2): 574-90.
[65]
Han X, Lamshöft M, Grobe N, et al. The biosynthesis of papaverine proceeds via (S)-reticuline. Phytochemistry 2010; 71(11-12): 1305-12.
[66]
Desgagné-Penix I, Facchini PJ. Systematic silencing of benzylisoquinoline alkaloid biosynthetic genes reveals the major route to papaverine in opium poppy. Plant J 2012; 72(2): 331-44.
[67]
Umar T, Hoda N. Selective inhibitors of phosphodiesterases: therapeutic promise for neurodegenerative disorders. MedChemComm 2015; 6: 2063-80.
[68]
Andersen OA, Schonfeld DL, Toogood-Johnson I, et al. Cross-linking of protein crystals as an aid in the generation of binary protein-ligand crystal complexes, exemplified by the human PDE10A-papaverine structure. Acta Crystallogr D Biol Crystallogr 2009; 65: 872-4.
[69]
Banerjee A, Narayana L, Raje FA, et al. Discovery of benzo[d]imidazo[5,1-b]thiazole as a new class of phosphodiesterase 10A inhibitors. Bioorganic Med Chem Lett 2013; 23(24): 6747-54.
[70]
Meegalla SK, Huang H, Illig CR, et al. Discovery of novel potent imidazo[1,2-b]pyridazine PDE10A inhibitors. Bioorganic Med Chem Lett 2016; 26(17): 4216-22.
[71]
Hamaguchi W, Masuda N, Miyamoto S, et al. Addressing phototoxicity observed in a novel series of biaryl derivatives: Discovery of potent, selective and orally active phosphodiesterase 10A inhibitor ASP9436. Bioorganic Med Chem 2015; 23(13): 3351-67.
[72]
Das BC, Thapa P, Karki R, et al. Boron chemicals in diagnosis and therapeutics. Future Med Chem 2013; 5(6): 653-76.
[73]
Soriano-Ursúa MA, Das BC, Trujillo-Ferrara JG. Boron-containing compounds: chemico-biological properties and expanding medicinal potential in prevention, diagnosis and therapy. Expert Opin Ther Pat 2014; 24(5): 485-500.
[74]
Farfán-García ED, Castillo-Mendieta NT, Ciprés-Flores FJ, Padilla-Martínez II, Trujillo-Ferrara JG, Soriano-Ursúa MA. Current data regarding the structure-toxicity relationship of boron-containing compounds. Toxicol Lett 2016; 258: 115-25.
[75]
Chłoń-Rzepa G, Jankowska AW, Zygmunt M, Pociecha K, Wyska E. Synthesis of 8-alkoxy-1,3-dimethyl-2,6-dioxopurin-7-yl-substituted acetohydrazides and butanehydrazides as analgesic and anti-inflammatory agents. Heterocycl Commun 2015; 21(5): 6-11.
[76]
Ho GD, Yang SW, Smotryski J, et al. The discovery of potent, selective, and orally active pyrazoloquinolines as PDE10A inhibitors for the treatment of Schizophrenia. Bioorganic Med Chem Lett 2012; 22(2): 1019-22.
[77]
Yang H, Murigi FN, Wang Z, Li J, Jin H, Tu Z. Synthesis and in vitro characterization of cinnoline and benzimidazole analogues as phosphodiesterase 10A inhibitors. Bioorganic Med Chem Lett 2014; 25(4): 919-24.
[78]
Kehler J, Ritzen A, Langgård M, et al. Triazoloquinazolines as a novel class of phosphodiesterase 10A (PDE10A) inhibitors. Bioorganic Med Chem Lett 2011; 21(12): 3738-42.
[79]
Bauer U, Giordanetto F, Bauer M, et al. Discovery of 4-hydroxy-1,6-naphthyridine-3-carbonitrile derivatives as novel PDE10A inhibitors. Bioorganic Med Chem Lett 2012; 22(5): 1944-8.
[80]
Burdi DF, Campbell JE, Wang J, et al. Evolution and synthesis of novel orally bioavailable inhibitors of PDE10A. Bioorganic Med Chem Lett 2015; 25(9): 1864-8.
[81]
Malamas MS, Ni Y, Erdei J, et al. Highly potent, selective, and orally active phosphodiesterase 10A inhibitors. J Med Chem 2011; 54(21): 7621-38.
[82]
Breslin MJ, Coleman PJ, Cox CD, et al. Amino tetrahydropyridopyrimidine
PDE10 inhibitor. US Patent 8691827 B2 April
8, 2014..
[83]
Coskran TM, Morton D, Menniti FS, et al. Immunohistochemical localization of phosphodiesterase 10A in multiple mammalian species. J Histochem Cytochem 2006; 54(11): 1205-13.
[84]
Seeger TF, Bartlett B, Coskran TM, et al. Immunohistochemical localization of PDE10A in the rat brain. Brain Res 2003; 985(2): 113-26.
[85]
Xie Z, Adamowicz WO, Eldred WD, et al. Cellular and subcellular localization of PDE10A, a striatum-enriched phosphodiesterase. Neuroscience 2006; 139(2): 597-607.
[86]
Graybiel AM. The basal ganglia and cognitive pattern generators. Schizophr Bull 1997; 23(3): 459-69.
[88]
Francis SH, Blount MA, Corbin JD. Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. Physiol Rev 2011; 91(2): 651-90.
[89]
Manni S, Mauban JH, Ward CW, Bond M. Phosphorylation of the cAMP-dependent protein kinase (PKA) regulatory subunit modulates PKA-AKAP interaction, substrate phosphorylation, and calcium signaling in cardiac cells. J Biol Chem 2008; 283(35): 24145-54.
[90]
Fajardo AM, Piazza GA, Tinsley HN. The role of cyclic nucleotide signaling pathways in cancer: Targets for prevention and treatment. Cancers (Basel) 2015; 6(1): 436-58.
[91]
Dremier S, Kopperud R, Doskeland SO, Dumont JE, Maenhaut C. Search for new cyclic AMP-binding proteins. FEBS Lett 2003; 546(1): 103-7.
[92]
Podda MV, Grassi C. New perspectives in cyclic nucleotide-mediated functions in the CNS: the emerging role of cyclic nucleotide-gated (CNG) channels. Pflugers Arch 2014; 466: 1241-57.
[93]
Woolfrey KM, Srivastava DP, Photowala H, et al. Epac2 induces synapse remodeling and depression and its disease-associated forms alter spines. Nat Neurosci 2009; 12: 1275-84.
[94]
Nishi A, Kuroiwa M, Shuto T. Mechanisms for the modulation of dopamine D1 receptor signaling in striatal neurons. Front Neuroanat 2011; 5: 43.
[95]
Polito M, Guiot E, Gangarossa G, et al. Selective effects of PDE10A inhibitors on striatopallidal neurons require phosphatase. eNeuro 2015; 2(4): 1-15.
[96]
Megens AA, Hendrickx HM, Hens KA, et al. Pharmacology of JNJ-42314415, a centrally active phosphodiesterase 10A (PDE10A) inhibitor: a comparison of PDE10A inhibitors with D2 receptor blockers as potential antipsychotic drugs. J Pharmacol Exp Ther 2014; 349(1): 138-54.
[97]
Smith SM, Uslaner JM, Cox CD, et al. The novel phosphodiesterase 10A inhibitor THPP-1 has antipsychotic-like effects in rat and improves cognition in rat and rhesus monkey. Neuropharmacol 2013; 64: 215-23.
[98]
Suzuki K, Harada A, Shiraishi E, Kimura H. In Vivo Pharmacological Characterization of TAK-063, a Potent and Selective Phosphodiesterase 10A Inhibitor with Antipsychotic-Like Activity in Rodents. J Pharmacol Exp Ther 2015; 352(3): 471-9.
[99]
Threlfell S, West AR. Modulation of striatal neuron activity by cyclic nucleotide signaling and phosphodiesterase inhibition. Basal Ganglia 2013; 3(3): 137-46.
[100]
Genoux D, Haditsch U, Knobloch M, Michalon A, Storm D, Mansuy IM. Protein phosphatase 1 is a molecular constraint on learning and memory. Nature 2002; 418(6901): 970-5.
[101]
Yang H, Hou H, Pahng A, et al. Protein Phosphatase-1 Inhibitor-2 Is a Novel Memory Suppressor. J Neurosci 2015; 35(45): 15082-7.
[102]
Li YW, Seager MA, Wojcik T, et al. Biochemical and behavioral effects of PDE10A inhibitors: Relationship to target site occupancy. Neuropharmacol 2016; 102: 121-35.
[103]
Jones PG, Hewitt MC, Campbell JE, et al. Pharmacological evaluation of a novel phosphodiesterase 10A inhibitor in models of antipsychotic activity and cognition. Pharmacol Biochem Behav 2015; 135: 46-52.
[104]
Grauer SM, Pulito VL, Navarra RL, et al. Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia. J Pharmacol Exp Ther 2009; 331(2): 574-90.
[105]
Sano H, Nagai Y, Miyakawa T, et al. Increased social interaction in mice deficient of the striatal medium spiny neuron-specific phosphodiesterase 10A2. J Neurochem 2008; 105(2): 546-56.
[106]
Piccart E, Gantois I, Laeremans A, et al. Impaired appetitively as
well as aversively motivated behaviors and learning in PDE10Adeficient
mice suggest a role for striatal signaling in evaluative
salience attribution. Neurobiol Learn Mem 2011. 95(3), 260(3):
260-9.
[107]
Assié MB, Carilla-Durand E, Bardin L, et al. The antipsychotics clozapine and olanzapine increase plasma glucose and corticosterone levels in rats: Comparison with aripiprazole, ziprasidone, bifeprunox and F15063. Eur J Pharmacol 2008; 592(1-3): 160-6.
[108]
Yee BK, Keist R, von Boehmer L, et al. A schizophrenia-related sensorimotor deficit links α3-containing GABAA receptors to a dopamine hyperfunction. Proc Natl Acad Sci USA 2005; 102(47): 17154-9.
[109]
Harada A, Suzuki K, Kimura H. 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. J Pharmacol Exp Ther 2017; 360(1): 75-83.
[111]
Giampà C, Patassini S, Borreca A, et al. Phosphodiesterase 10 inhibition reduces striatal excitotoxicity in the quinolinic acid model of Huntington’s disease. Neurobiol Dis 2009; 34(3): 450-6.
[112]
García AM, Brea J, González-García A, et al. Targeting PDE10A GAF domain with small molecules: A way for allosteric modulation with anti-inflammatory effects. Molecules 2017; 22(9): E1472.
[113]
Andrés JI, Buijnsters P, De Angelis M, et al. Discovery of a new series of [1,2,4]triazolo[4,3-a]quinoxalines as dual phosphodiesterase 2/phosphodiesterase 10 (PDE2/PDE10) inhibitors. Bioorganic Med Chem Lett 2013; 23(3): 785-90.
[114]
Redrobe JP, Rasmussen LK, Christoffersen CT, Bundgaard C, Jørgensen M. Characterisation of Lu AF33241: A novel, brain-penetrant, dual inhibitor of phosphodiesterase (PDE) 2A and PDE10A. Eur J Pharmacol 2015; 761: 79-85.
[116]
Chłoń-Rzepa G, Zagórska A, Żmudzki P, et al. Aminoalkyl Derivatives of 8-Alkoxypurine-2,6-diones: Multifunctional 5-HT1A/5-HT7 Receptor Ligands and PDE Inhibitors with Antidepressant Activity. Arch Pharm (Weinheim) 2016; 349(12): 889-903.
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