Phosphodiesterase 10A inhibitors as a novel therapeutic approach for schizophrenia

Expert Opinion on Drug Discovery

Volumn 2, Issue 7, 2007, Pages 1001-1009

  Siuciak, Judith A ^a,b   Strick, Christine A ^b  

^a PFIZER INC   (United States)

^b BRISTOL MYERS SQUIBB   (United States)

Author keywords

Basal ganglia; Huntington's disease; Medium spiny neuron; Phosphodiesterase; Psychosis; Schizophrenia; Striatum

Indexed keywords

2 [4 (1 METHYL 4 PYRIDIN 4 YL 1H PYRAZOL 3 YL)]PHENOXYMETHYLQUINOLINE; 2 [4 [ PYRIDIN 4 YL 1 (2,2,2 TRIFLUOROETHYL) 1H PYRAZOL 3 YL]PHENOXYMETHYL]QUINOLINESUCCINIC ACID; 6,7 DIMETHOXY 4 [3 (QUINOXALIN 2 YLOXY)PYRROLIDIN 1 YL]QUINAZOLINE; AMPHETAMINE; ATYPICAL ANTIPSYCHOTIC AGENT; CENTRAL NERVOUS SYSTEM AGENTS; CLOZAPINE; DIMETHOXYPYRROLIDYLQUINAZOLINE; DIPYRIDAMOLE; DOPAMINE RECEPTOR BLOCKING AGENT; HALOPERIDOL; ISOBUTYLMETHYLXANTHINE; MESSENGER RNA; METHAMPHETAMINE; MP 10; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NEUROLEPTIC AGENT; PAPAVERINE; PHOSPHODIESTERASE; PHOSPHODIESTERASE 10A INHIBITOR; PHOSPHODIESTERASE INHIBITOR; PQ 10; RISPERIDONE; ROLIPRAM; TP 10; UNCLASSIFIED DRUG; ZIPRASIDONE;

AMINO TERMINAL SEQUENCE; CARBOXY TERMINAL SEQUENCE; CARDIOVASCULAR DISEASE; CATALYSIS; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL TRIAL; DRUG EFFECT; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG POTENCY; DRUG RESPONSE; DRUG SAFETY; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME INHIBITION; ENZYME LOCALIZATION; ENZYME PHOSPHORYLATION; EXTRAPYRAMIDAL SYMPTOM; GENETIC CODE; HUMAN; HYPERTENSION; IMPAIRED GLUCOSE TOLERANCE; LOW DRUG DOSE; METABOLIC DISORDER; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FAMILY; REVIEW; SCHIZOPHRENIA; VOMITING;

EID: 34547396908     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460441.2.7.1001     Document Type: Review

References (63)

1. LIEBERMAN JA, STROUP TS, MCEVOY JP et al.: Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. (2005) 353:1209-1223.
2. MELTZER HY, BOBO WV: Interpreting the efficacy findings in the CATIE study: what clinicians should know. CNS spectr. (2006) 11:14-24.
3. SODERLING SH, BEAVO JA: Regulation of cAMP and cGMP signaling: new phosphodiesterases and new functions. Curr. Opin. Cell Biol. (2000) 12:174-179.
4. BENDER AT, BEAVO JA: Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol. Rev. (2006) 58:488-520.
5. BEAVO JA, HOUSLAY MD, FRANCIS SH: Cyclic nucleotide phosphodiesterase superfamily. In: Cyclic Nucleotide Phosphodiesterases in Health and Disease. Beavo JA, Francis SH, Houslay MD (Eds), CRC Press, Boca Raton (2007):3-17.
6. SODERLING SH, BAYUGA SJ, BEAVO JA: Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A. Proc. Natl. Acad. Sci. USA (1999) 96:7071-7076.
7. 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) 234:109-117.
8. FUJISHIGE K, KOTERA J, MICHIBATA H et al.: Cloning and charactetizadon of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A). J. Biol. Chem. (1999) 274:18438-18445.
9. STROOP SD, CHARBONNEAU H, BEAVO JA: Direct photolabeling of the cGMP-stimulated cyclic nucleotide phosphodiesterase. J. Biol. Chem. (1989) 15:13718-13725.
10. MCALLISTER-LUCAS LM, HAIK TL, COLBRAN JL et al.: An essential aspanic acid at each of two allosteric cGMP-binding sites of a cGMP-specific phosphodiesterase. J. Biol. Chem. (1995) 270:30671-30679.
11. GILLESPIE PG, BEAVO JA: cGMP is tightly bound to bovine retinal rod phosphodiesterase. Proc. Natl. Acad. Sci. USA (1989) 86:4311-4315.
12. GROSS-LANGENHOFF M, HOFBAUER K, WEBER J, SCHULTZ A, SCHULTZ JE: 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) 281:2841-2846.
13. FUJISHIGE K, KOTERA J, OMORI K: Striatum- and testis-specific phosphodiesterase PDE10A. Isolation and characterization of a rat PDE10A. Eur. J. Biochem. (1999) 266:1118-1127.
14. 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) 261:551-557.
15. O'CONNOR V, GENIN A, DAVIS S et al.: Differential amplification of intron-containing transcripts reveals long term potentiation-associated up-regulation of specific PDE10A phosphodiesterase splice variants. J. Biol. Chem. (2004) 279:15841-15849.
16. 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) 279:4366-4375.
17. SEEGER TF, BARTLETT B, COSKRAN TM et al.: Immunohistochemical localization of PDE10A in the rat brain. Brain Res. (2003) 985:113-126.
18. XIE Z, ADAMOWICZ WO, ELDRED WD et al.: Cellular and subcellular localization of PDE10A, a striatum-enriched phosphodiesterase. Neuroscience (2006) 139:597-607.
19. COSKRAN TM, MORTON D, MENNITI FS et al.: Immunohistochemical localization of phosphodiesterase PDE10A in multiple mammalian species. J. Histochem. Cytochem. (2006) 54:1205-1213.
20. RING HA, SERRA-MESTRES J: Neuropsychiatry of the basal ganglia. J. Neural Neurosurg. Psychiatry (2002) 72:12-21.
21. GRAYBIEL AM: The basal ganglia. Curr. Biol. (2000) 10:R509-R511.
22. SIUCIAK JA, MCCARTHY SA, CHAPIN DS et al.: Genetic deletion of the striatum-enriched phosphodiesterase PDE10A: evidence for altered striatal function. Neuropharmacology (2006) 51:374-385.
23. SIUCIAK JA, CHAPIN DS, HARMS JF et al.: Inhibition of the striatum-enriched phosphodiesterase PDE10A: a novel approach to the treatment of psychosis. Neuropharmacology (2006) 51:386-396.
24. MERCK GM: Vorläufige Notiz über eine neue organische Base im Opium. Ann. (1848) 66:125-128.
25. PICTET A, GAMS A: Comptes rendus hebdomadaires des séances de l'Académie des sciences (1909) 149:210-212.
26. SCHIFF PL: Opium and its alkaloids. Am. J. Pharm. Educ. (2002) 66:186-194.
27. CHAPPIE TA, HUMPHREY JM, ALLEN MP et al.: Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors. J. Med. Chem. (2007) 50:182-185.
28. SIUCIAK JA, CHAPIN DS, MCCARTHY SA et al.: Novel potent and selective phosphodiesterase 10A (PDE10A) inhibitors show activity in animal models of psychosis. Neuroscience Meeting Planner, Society for Neuroscience (2006).
29. SIUCIAK JA, CHAPIN DS, MCCARTHY SA et al.: Novel potent and selective PDE10A inhibitors show activity in animal models of psychosis and anxiety. Schizophrenia Bulletin (2007) 33:479.
30. JAMES LC, FOX CB, CHAPPIE T et al.: Induction of striatal gene expression by PDE10A inhibitors. Neuroscience Meeting Planner, Society for Neuroscience (2006).
31. LINDHOLM E, EKHOLM B, SHAW S et al.: A schizophrenia-susceptibility locus at 6q25, in one of the world's largest reported pedigrees. Am. J. Hum. Genet. (2001) 69:96-105.
32. KAPUR S: Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am. J. Psychiatry (2003) 160:13-23.
33. WADENBERG ML, HICKS PB: The conditioned avoidance response test re-evaluated: is it a sensitive test for the detection of potentially atypical antipsychotics? Neurosci. Biobehav. Rev. (1999) 23:851-862.
34. TAMMINGA CA: The neurobiology of cognition in schizophrenia. Schizo cog review. J. Clin. Psychiatry (2006) 67:9-13.
35. FUJII DE, WYLIE AM: Neurocognition and community outcome in schizophrenia: long-term predictive validity. Schizophr. Res. (2003) 59:219-223.
36. RODEFER JS, MURPHY ER, BAXTER MG: PDE10A inhibition reverses subchronic PCP-induced deficits in attentional set-shifting in rats. J. Neurosci. (2005) 21:1070-1076.
37. JENTSCH JD, ROTH RH: The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology (1999) 20:201-225.
38. LIU F, ZHANG G, KELLEY C, DAY M, MARQUIS K, BRANDON N: Biochemical analysis of mechanism action of PDE10A inhibitor papaverine in pro-cognitive effects. Neuroscience Meeting Planner, Society for Neuroscience (2006).
39. NEWCOMER JW: Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J. Clin. Psychiatry (2007) 68:20-27.
40. KELLEY AE: Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning. Neurosci. Biobehav. Rev. (2004) 27:765-776.
41. BLACK SC, GIBBS M, MCNEISH JD et al.: Genetic deletion of phosphodiesterase 10A results in a phenotype of resistance to high fat diet-induced obesity, elevated circulating adiponectin and improved glucose tolerance: a new drug target. Keystone Symposium Abstracts, Adipogenesis, Obesity and Inflammation (2006):149.
42. POLLI JW, KINCAID RL: Molecular cloning of DNA encoding a calmodulin-dependent phosphodiesterase enriched in striatum. Proc. Natl. Acad. Sci. USA (1992) 89:11079-11083.
43. YAN C, BENTLEY JK, SONNENBURG WK, BEAVO JA: Differential expression of the 61 kDa and 63 kDa calmodulin-dependent phosphodiesterases in the mouse brain. J. Neurosci. (1994) 14:973-984.
44. VAN STAVEREN WC, STEINBUSCH HW, MARKERINK-VAN ITTERSUM M et al.: mRNA expression patterns of the cGMP-hydrolyzing phosphodiesterases types 2, 5, and 9 during development of the rat brain. J. Comp. Neural (2003) 467:566-580.
45. JUILFS DM, SODERLING S, BURNS F, BEAVO JA: Cyclic GMP as substrate and regulator of cyclic nucleotide phosphodiesterases (PDEs). Rev. Physiol. Biochem. (1999) 135:67-104.
46. CHERRY JA, DAVIS RL: Cyclic AMP phosphodiesterases are localized in regions of the mouse brain associated with reinforcement, movement, and affect. J. Comp. Neurol. (1999) 407:287-301.
47. CHO CH, CHO DH, SEO MR, JUHNN YS: Differential changes in the expression of cyclic nucleotide phosphodiesterase isoforms in rat brains by chronic treatment with electroconvulsive shock. Exp. Mol. Med. (2000) 32:110-114.
48. SASAKI T, KOTERA J, OMORI K: Novel alternative splice variants of rat phosphodiesterase 7B showing unique tissue-specific expression and phosphorylation. Biochem. J. (2002) 361:211-220.
49. REYES-IRISARRI E, PEREZ-TORRES S, MENGOD G: Neuronal expression of cAMP-specific phosphodiesterase 7B mRNA in the rat brain. Neuroscience (2005) 132:1173-1185.
50. KANES SJ, TOKARCZYK J, SIEGEL SJ, BILKER W, ABEL T, KELLY MP: Rolipram: a specific phosphodiesterase 4 inhibitor with potential antipsychotic activity. Neuroscience (2007) 144:239-246.
51. DAVIS JA, GOULD TJ: Rolipram attenuates MK-801-induced deficits in latent inhibition. Behav. Neurosci. (2005) 119:595-602.
52. MORI T, BABA J, ICHIMARU Y, SUZUKI T: Effects of rolipram, a selective inhibitor of phosphodiesterase 4, on hyperlocomotion induced by several abused drugs in mice. Jpn. J. Pharmacol. (2000) 83:113-118.
53. 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. Psychopharmacology (2007) 192:415-424.
54. CHAPIN DS, MCCARTHY SA, MARTIN AN, SIUCIAK JA: Rolipram, a PDE4 inhibitor, shows efficacy in animal models of antipsychotic-like activity: studies using PDE4B and PDE4D knockout mice. Schizophrenia Bulletin (2007) 33:470.
55. ROSE GM, HOPPER A, DE VIVO M, TEHIM A: Phosphodiesterase inhibitors for cognitive enhancement. Curr. Pharm. Des. (2005) 11:3329-3334.
56. PIETZCKER A, MULLER-OERLINGHAUSEN B, KEHR W: Antipsychotic activity of rolipram in schizophrenic patients. A pilot study. Naunyn-Schmiedebergs Arch. Pharmacol. (1979) 308:R44.
57. MIRO X, PEREZ-TORRES S, PUIGDOMENECH P, PALACIOS JM, MENGOD G: Differential distribution of PDE4D splice variant mRNAs in rat brain suggests association with specific pathways and presynaptical localization. Synapse (2002) 45:259-269.
58. REED TM, BROWNING JE, BLOUGH RI, VORHEES CV, REPASKE DR: Genomic structure and chromosome location of the murine PDE1B phosphodiesterase gene. Mamm. Genome (1998) 9:571-576.
59. SIUCIAK JA, MCCARTHY SA, CHAPIN DS, REED TM, VORHEES CV, REPASKE DR: Behavioral and neurochemical characterization of mice deficient in the phosphodiesterase-1B (PDE1B) enzyme. Neuropharmacology (2007) [Epub ahead of print].
60. EHRMAN LA, WILLIAMS MT, SCHAEFER TL et al.: Phosphodiesterase 1B differentially modulates the effects of methamphetamineon locomotor activity and spatial learning through DARPP32-dependent pathways: evidence from PDE1B-DARPP32 double-knockout mice. Genes Brain Behav. (2006) 5:540-551.
61. MELONE MAB, JORI FP, PELUSO G: Huntington's disease: new frontiers for molecular and cell therapy. Curr. Drug Targets (2005) 6:43-56.
62. HEBB ALO, ROBERTSON HA, DENOVAN-WRIGHT EM: Striatal phosphodiesterase mRNA and protein levels are reduced in Huntington's disease transgenic mice prior to the onset of motor symptoms. Neuroscience (2004) 123:967-981.
63. HU H, MCCAW EA, HEBB ALO, GOMEZ GT, DENOVAN-WRIGHT EM: Mutant huntintin affects the rat of transcription of striatum-speciticisoforms of phophodiesterase 10A. Eur. J. Neurosci. (2004) 20:3351-3363.