Targeting PDE10A in schizophrenia

Drugs of the Future

Volumn 37, Issue 8, 2012, Pages 577-589

  Hoefgen, N ^a   Grunwald, C ^a   Langen, B ^a   Hoefgen, Norbert ^a  

^a Biocrea GmbH   (Germany)

Author keywords

Dopaminergic system; Glutamatergic system; PDE10A; Phosphodiesterase inhibitors; Schizophrenia

Indexed keywords

2 [4 [1 METHYL 4 (4 PYRIDINYL) 3 PYRAZOLYL]PHENOXYMETHYL]QUINOLINE; CLOZAPINE; GLUTAMINE; HALOPERIDOL; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NEUROLEPTIC AGENT; OLANZAPINE; PAPAVERINE; PHOSPHODIESTERASE; PHOSPHODIESTERASE 10; PHOSPHODIESTERASE 10 INHIBITOR; PHOSPHODIESTERASE INHIBITOR; SCH 1518291; TP 10; TYROSINE; UNCLASSIFIED DRUG; WEB 3; WEB 6;

COGNITION; DRUG BINDING; DRUG EFFICACY; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME INHIBITION; ENZYME STRUCTURE; EXTRAPYRAMIDAL SYMPTOM; HUMAN; HYPERPROLACTINEMIA; METABOLIC SYNDROME X; NONHUMAN; REVIEW; SCHIZOPHRENIA; SIDE EFFECT; WEIGHT GAIN;

EID: 84952982097     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.2012.037.08.1805929     Document Type: Review

References (88)

1. Benes, F.M. The relationship between structural brain imaging and histopathologic findings in schizophrenia research. Harv Rev Psychiatry 1993, 1(2): 100-9.
2. Rummel-Kluge, C., Komossa, K., Schwarz, S. et al. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: A systematic review and meta-analysis. Schizophr Res 2010, 123(2-3): 225-33.
3. Gardner, D.M., Baldessarini, R.J., Waraich, P. Modern antipsychotic drugs: A critical overview. CMAJ 2005, 172(13): 1703-11. (Pubitemid 40896865)
4. Lieberman, J.A., Stroup, T.S., McEvoy, J.P. et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005, 353(12): 1209-23. (Pubitemid 41345943)
5. Essayan, D.M. Cyclic nucleotide phosphodiesterases . J Allergy Clin Immunol 2001, 108(5): 671-80. (Pubitemid 33096193)
6. Soderling, S.H., Bayuga, S.J., Beavo, J.A. Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A. Proc Natl Acad Sci U S A 1999, 96(12): 7071-6. (Pubitemid 29275011)
7. Fabbri, L.M., Beghé, B., Yasothan, U., Kirkpatrick, P. Fresh from the pipeline: Roflumilast. Nat Rev Drug Discov 2010, 9(10): 761-2.
8. Menniti, F.S., Faraci, W.S., Schmidt, C.J. Phosphodiesterases in the CNS: Targets for drug development. Nat Rev Drug Discov 2006, 5(8): 660-70. (Pubitemid 44151604)
9. Reneerkens, O.A., Rutten, K., Steinbusch, H.W., Blokland, A., Prickaerts, J. Selective phosphodiesterase inhibitors: A promising target for cognition enhancement. Psychopharmacology (Berl) 2009, 202(1-3): 419-43.
10. Menniti, F., Stick, C.A., Seeger, T.F., Ryan, A.M. Immunohistochemical localization of PDE10 in the rat brain . William Harvey Research Conference 'Phosphodiesterase in Health and Disease', Porto, Portugal 2001.
11. Seeger, T.F., Bartlett, B., Coskran, T.M. et al. Immunohistochemical localization of PDE10A in the rat brain. Brain Res 2003, 985(2): 113-26. (Pubitemid 37088176)
12. Coskran, T.M., Morton, D., Menniti, F.S. et al. Immunohistochemical localization of phosphodiesterase 10A in multiple mammalian species . J Histochem Cytochem 2006, 54(11): 1205-13. (Pubitemid 44623341)
13. Xie, Z., Adamowicz, W.O., Eldred, W.D. et al. Cellular and subcellular localization of PDE10A, a striatum-enriched phosphodiesterase. Neuroscience 2006, 139(2): 597-607.
14. Siuciak, J.A., Chapin, D.S., Harms, J.F. et al. Inhibition of the striatumenriched phosphodiesterase PDE10A: A novel approach to the treatment of psychosis. Neuropharmacology 2006, 51(2): 386-96. (Pubitemid 44061894)
15. Siuciak, J.A., McCarthy, S.A., Chapin, D.S. et al. Genetic deletion of the striatum-enriched phosphodiesterase PDE10A: Evidence for altered striatal function. Neuropharmacology 2006, 51(2): 374-85. (Pubitemid 44061880)
16. Schmidt, C.J., Chapin, D.S., Cianfrogna, J. et al. Preclinical characterization of selective phosphodiesterase 10A inhibitors: A new therapeutic approach to the treatment of schizophrenia. J Pharmacol Exp Ther 2008, 325(2): 681-90. (Pubitemid 351574819)
17. 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. (Pubitemid 38199025)
18. Kellendonk, C., Simpson, E.H., Polan, H.J. et al. Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning. Neuron 2006, 49(4): 603-15. (Pubitemid 43221894)
19. Soderling, S.H., Beavo, J.A. Regulation of cAMP and cGMP signaling: New phosphodiesterases and new functions. Curr Opin Cell Biol 2000, 12(2): 174-9. (Pubitemid 30142563)
20. Kaiya, H. Second messenger imbalance hypothesis of schizophrenia. Prostaglandins Leukot Essent Fatty Acids 1992, 46(1): 33-8.
21. Muly, C. Signal transduction abnormalities in schizophrenia: The cAMP system. Psychopharmacol Bull 2002, 36(4): 92-105.
22. Garver, D.L., Johnson, C., Kanter, D.R. Schizophrenia and reduced cyclic AMP production: Evidence for the role of receptor-linked events. Life Sci 1982, 31(18): 1987-92. (Pubitemid 13209947)
23. Leveque, J.C., Macias, W., Rajadhyaksha, A. et al. Intracellular modulation of NMDA receptor function by antipsychotic drugs. J Neurosci 2000, 20(11): 4011-20. (Pubitemid 30365671)
24. Gattaz, W.F., Cramer, H., Beckmann, H. Haloperidol increases the cerebrospinal fluid concentrations of cyclic GMP in schizophrenic patients. Biol Psychiatry 1984, 19(8): 1229-35. (Pubitemid 14014785)
25. Grauer, S.M., Pulito, V.L., Navarra, R.L. 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.
26. Capuano, B., Crosby, I.T., Lloyd, E.J. Schizophrenia: Genesis, receptorology and current therapeutics. Curr Med Chem 2002, 9(5): 521-48. (Pubitemid 34436433)
27. Nyberg, S., Olsson, H., Nilsson, U., Maehlum, E., Halldin, C., Farde, L. Low striatal and extra-striatal D(2) receptor occupancy during treatment with the atypical antipsychotic sertindole. Psychopharmacology (Berl) 2002, 162(1): 37-41. (Pubitemid 34639554)
28. Newcomer, J.W., Farber, N.B., Jevtovic-Todorovic, V. et al. Ketamine-induced NMDA receptor hypofunction as a model of memory impairment and psychosis. Neuropsychopharmacology 1999, 20(2): 106-18. (Pubitemid 29010370)
29. Jentsch, J.D., Roth, R.H. The neuropsychopharmacology of phencyclidine: From NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 1999, 20(3): 201-25. (Pubitemid 29067401)
30. Langen, B., Dost, R., Egerland, U., Stange, H., Hoefgen, N. Effect of PDE10A inhibitors on MK-801-induced immobility in the forced swim test. Psychopharmacology (Berl) 2012, 221(2): 249-59.
31. Sams-Dodd, F. Phencyclidine-induced stereotyped behaviour and social isolation in rats: A possible animal model of schizophrenia. Behav Pharmacol 1996, 7(1): 3-23. (Pubitemid 26051782)
32. Garey, R.E. PCP (phencyclidine): An update. J Psychedelic Drugs 1979, 11(4): 265-75. (Pubitemid 10164484)
33. Allen, R.M., Young, S.J. Phencyclidine-induced psychosis. Am J Psychiatry 1978, 135(9): 1081-4. (Pubitemid 8395441)
34. Sano, H., Nagai, Y., Miyakawa, T., Shigemoto, R., Yokoi, M. Increased social interaction in mice deficient of the striatal medium spiny neuron-specific phosphodiesterase 10A2. J Neurochem 2008, 105(2): 546-56. (Pubitemid 351490018)
35. Young, J.W., Powell, S.B., Risbrough, V., Marston, H.M., Geyer, M.A. Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia. Pharmacol Ther 2009, 122(2): 150-202.
36. Barnett, J.H., Robbins, T.W., Leeson, V.C., Sahakian, B.J., Joyce, E.M., Blackwell, A.D. Assessing cognitive function in clinical trials of schizophrenia. Neurosci Biobehav Rev 2010, 34(8): 1161-77.
37. Rodefer, J.S., Murphy, E.R., Baxter, M.G. PDE10A inhibition reverses subchronic PCP-induced deficits in attentional set-shifting in rats. Eur J Neurosci 2005, 21(4): 1070-6. (Pubitemid 40461058)
38. Rodefer,J.S., Saland,S.K., Eckrich,S.J. Selective phosphodiesterase inhibitors improve performance on the ED/ID cognitive task in rats. Neuropharmacology 2012, 62(3): 1182-1190.
39. Adler, L.E., Pachtman, E., Franks, R.D., Pecevich, M., Waldo, M.C., Freedman, R. Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. Biol Psychiatry 1982, 17(6): 639-54. (Pubitemid 12090209)
40. Geyer, M.A., Swerdlow, N.R., Mansbach, R.S., Braff, D.L. Startle response models of sensorimotor gating and habituation deficits in schizophrenia. Brain Res Bull 1990, 25(3): 485-98. (Pubitemid 20346586)
41. Braver, T.S., Barch, D.M., Cohen, J.D. Cognition and control in schizophrenia: A computational model of dopamine and prefrontal function. Biol Psychiatry 1999, 46(3): 312-28. (Pubitemid 29335912)
42. Light, G.A., Braff, D.L. Human and animal studies of schizophrenia- related gating deficits. Curr Psychiatry Rep 1999, 1(1): 31-40.
43. Newcomer, J.W. Second-generation (atypical) antipsychotics and metabolic effects: A comprehensive literature review. CNS Drugs 2005, 19(Suppl. 1):1-93. (Pubitemid 40677047)
44. Black, S.C., Gibbs, E.M. (Pfizer, Inc.) Phosphodiesterase 10 inhibition as treatment for obesity-related and metabolic syndrome-related conditions. WO 2005120514.
45. Cantin, L.D., Magnuson, S., Gunn, D. et al. PDE-10A inhibitors as insulin secretagogues. Bioorg Med Chem Lett 2007, 17(10): 2869-73. (Pubitemid 46636247)
46. Sotty, F., Montezinho, L.P., Steiniger-Brach, B., Nielsen, J. Phosphodiesterase 10A inhibition modulates the sensitivity of the mesolimbic dopaminergic system to D-amphetamine: Involvement of the D1-regulated feedback control of midbrain dopamine neurons. J Neurochem 2009, 109(3): 766-75.
47. Dedeurwaerdere, S., Wintmolders, C., Vanhoof, G., Langlois, X. Patterns of brain glucose metabolism induced by phosphodiesterase 10A inhibitors in the mouse: A potential translational biomarker. J Pharmacol Exp Ther 2011, 339(1): 210-7.
48. Nishi, A., Kuroiwa, M., Miller, D.B. et al. Distinct roles of PDE4 and PDE10A in the regulation of cAMP/PKA signaling in the striatum. J Neurosci 2008, 28(42): 10460-71.
49. Nishi, A., Kuroiwa, M., Shuto, T. Mechanisms for the modulation of dopamine d(1) receptor signaling in striatal neurons. Front Neuroanat 2011, 5: 43.
50. Threlfell, S., Sammut, S., Menniti, F.S., Schmidt, C.J., West, A.R. Inhibition of phosphodiesterase 10A increases the responsiveness of striatal projection neurons to cortical stimulation. J Pharmacol Exp Ther 2009, 328(3): 785-95.
51. Charych, E.I., Jiang, L.X., Lo, F., Sullivan, K., Brandon, N.J. 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.
52. Matthiesen, K., Nielsen, J. Cyclic AMP control measured in two compartments in HEK293 cells: phosphodiesterase K(M) is more important than phosphodiesterase localization. PLoS One 2011, 6(9): e24392.
53. Conti, M., Beavo, J. Biochemistry and physiology of cyclic nucleotide phosphodiesterases: Essential components in cyclic nucleotide signaling. Annu Rev Biochem 2007, 76: 481-511.
54. Fujishige, K., Kotera, J., Michibata, H., Yuasa, K., Takebayashi, S., Okumura, K., Omori, K. Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A). J Biol Chem 1999, 274(26): 18438-18445.
55. 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(3): 551-7. (Pubitemid 29408096)
56. Gross-Langenhoff, M., Hofbauer, K., Weber, J., Schultz, A., Schultz, J.E. cAMP is a ligand for the tandem GAF domain of human phosphodiesterase 10 and cGMP for the tandem GAF domain of phosphodiesterase 11. J Biol Chem 2006, 281(5): 2841-6. (Pubitemid 43845749)
57. Matthiesen, K., Nielsen, J. Binding of cyclic nucleotides to phosphodiesterase 10A and 11A GAF domains does not stimulate catalytic activity. Biochem J 2009, 423(3): 401-9.
58. Jaeger, R., Russwurm, C., Schwede, F., Genieser, H.G., Koesling, D., Russwurm, M. Activation of PDE10 and PDE11 phosphodiesterases. J Biol Chem 2012, 287(2): 1210-9.
59. Handa, N., Mizohata, E., Kishishita, S. et al. Crystal structure of the GAFB domain from human phosphodiesterase 10A complexed with its ligand, cAMP. J Biol Chem 2008, 283(28): 19657-64.
60. Wang, H., Liu, Y., Hou, J., Zheng, M., Robinson, H., Ke, H. Structural insight into substrate specificity of phosphodiesterase 10. Proc Natl Acad Sci U S A 2007, 104(14): 5782-7. (Pubitemid 47175611)
61. Zhang, K.Y., Card, G.L., Suzuki, Y. et al. A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases. Mol Cell 2004, 15(2): 279-86. (Pubitemid 38950974)
62. Chappie, T.A., Humphrey, J.M., Allen, M.P. et al. Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors. J Med Chem 2007, 50(2): 182-5. (Pubitemid 46147698)
63. Card, G.L., Blasdel, L., England, B.P. et al. A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design. Nat Biotechnol 2005, 23(2): 201-7. (Pubitemid 40255330)
64. Conti, M. A view into the catalytic pocket of cyclic nucleotide phosphodiesterases. Nat Struct Mol Biol 2004, 11(9): 809-10. (Pubitemid 39128795)
65. Huai, Q., Sun, Y., Wang, H. et al. Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase. J Med Chem 2006, 49(6): 1867-73.
66. Kehler, J., Nielsen, J. PDE10A inhibitors: Novel therapeutic drugs for schizophrenia. Curr Pharm Des 2011, 17(2): 137-50.
67. Wang, H., Robinson, H., Ke, H. The molecular basis for different recognition of substrates by phosphodiesterase families 4 and 10. J Mol Biol 2007, 371(2): 302-7. (Pubitemid 47048279)
68. Pandit, J. (Pfizer, Inc.). Crystal structure of 3′,5′-cyclic nucleotide phosphodiesterase (PDE10A) and uses thereof. Patent US 20050202550.
69. Andersen, O.A., Schonfeld, D.L., 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(Pt. 8): 872-4.
70. Chappie, T., Humphrey, J., Menniti, F., Schmidt, C. PDE10A inhibitors: An assessment of the current CNS drug discovery landscape. Curr Opin Drug Discov Devel 2009, 12(4): 458-67.
71. Ho, G.D., Michael, S.W., Bercovici, A. et al. The SAR development of dihydroimidazoisoquinoline derivatives as phosphodiesterase 10A inhibitors for the treatment of schizophrenia. Bioorg Med Chem Lett 2012, 22(7): 2585-9.
72. Hu, E., Kunz, R.K., Rumfelt, S. et al. Discovery of potent, selective, and metabolically stable 4-(pyridin-3-yl)cinnolines as novel phosphodiesterase 10A (PDE10A) inhibitors. Bioorg Med Chem Lett 2012, 22(6): 2262-5.
73. Zhang, Z., Lu, X., Xu, J., Rothfuss, J., Mach, R.H., Tu, Z. Synthesis and in vitro evaluation of new analogues as inhibitors for phosphodiesterase 10A. Eur J Med Chem 2011, 46(9): 3986-95.
74. rd Natl Meet ACS (March 25-29, San Diego) 2012, Abst MEDI 24.
75. Malamas, M.S., Ni, Y., Erdei, J. et al. Highly potent, selective, and orally active phosphodiesterase 10A inhibitors. J Med Chem 2011, 54(21): 7621-38.
76. Verhoest, P.R., Chapin, D.S., 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.
77. Helal, C.J., Kang, Z., Hou, X. et al. Use of structure-based design to discover a potent, selective, in vivo active phosphodiesterase 10A inhibitor lead series for the treatment of schizophrenia. J Med Chem 2011, 54(13): 4536-47.
78. McElroy, W.T., Tan, Z., Basu, K. et al. Pyrazoloquinolines as PDE10A inhibitors: Discovery of a tool compound. Bioorg Med Chem Lett 2012, 22(3): 1335-9.
79. Yang, S.W., Smotryski, J., McElroy, W.T. et al. Discovery of orally active pyrazoloquinolines as potent PDE10 inhibitors for the management of schizophrenia. Bioorg Med Chem Lett 2012, 22(1): 235-9.
80. Ho, G.D., Yang, S.W., Smotryski, J. et al. The discovery of potent, selective, and orally active pyrazoloquinolines as PDE10A inhibitors for the treatment of schizophrenia. Bioorg Med Chem Lett 2012, 22(2): 1019-22.
81. Höfgen, N., Stange, H., Schindler, R. et al. Discovery of imidazo[1,5-a]pyrido[ 3,2-e]pyrazines as a new class of phosphodiesterase 10A inhibitors. J Med Chem 2010, 53(11): 4399-411.
82. Bauer, U., Giordanetto, F., Bauer, M. et al. Discovery of 4-hydroxy-1,6- naphthyridine-3-carbonitrile derivatives as novel Pde10A inhibitors. Bioorg Med Chem Lett 2012, 22(5): 1944-8.
83. Kehler, J., Ritzen, A., Langgard, M. et al. Triazoloquinazolines as a novel class of phosphodiesterase 10A (PDE10A) inhibitors. Bioorg Med Chem Lett 2011, 21(12): 3738-42.
84. Asproni, B., Murineddu, G., Pau, A. et al. Synthesis and SAR study of new phenylimidazole-pyrazolo[1,5-c]quinazolines as potent phosphodiesterase 10A inhibitors. Bioorg Med Chem 2011, 19(1): 642-9.
85. An inpatient study of the efficacy, safety, and tolerability of PF-02545920 in the treatment of acute exacerbation of schizophrenia (NCT01175135). ClinicalTrials.gov Web site, June 11, 2012.
86. Pfizer study. Effects of PF-02545920 on ketamine-induced abnormal prefrontal brain response to associative learning in healthy subjects (NCT01244880).ClinicalTrials.gov Web site, June 11, 2012.
87. Laskowski, R.A., Swindells, M.B. LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model 2011, 51(10): 2778-86.
88. Yang, S.W., Smotryski, J., McElroy, W.T. et al. Discovery of orally active pyrazoloquinolines as potent PDE10 inhibitors for the management of schizophrenia. Bioorg Med Chem Lett 2012, 22(1): 235-9.