Characterisation of Lu AF33241: A novel, brain-penetrant, dual inhibitor of phosphodiesterase (PDE) 2A and PDE10A

European Journal of Pharmacology

Volumn 761, Issue , 2015, Pages 79-85

  Redrobe, John P ^a   Rasmussen, Lars K ^a   Christoffersen, Claus T ^a   Bundgaard, Christoffer ^a   Jørgensen, Morten ^a  

^a H LUNDBECK A S   (Denmark)

Author keywords

Antipsychotic; Cognition; Inhibitor; PDE10A; PDE2A; Schizophrenia

Indexed keywords

2 [4 [1 METHYL 4 (4 PYRIDINYL) 3 PYRAZOLYL]PHENOXYMETHYL]QUINOLINE; HALOPERIDOL; LU AF 33241; NEUROLEPTIC AGENT; PHENCYCLIDINE; PHOSPHODIESTERASE; PHOSPHODIESTERASE 10A; PHOSPHODIESTERASE 1C; PHOSPHODIESTERASE 2A; PHOSPHODIESTERASE 3A; PHOSPHODIESTERASE 4D; PHOSPHODIESTERASE 5A; PHOSPHODIESTERASE 6B; PHOSPHODIESTERASE 7B; PHOSPHODIESTERASE 8A; PHOSPHODIESTERASE 9A; PHOSPHODIESTERASE11A; UNCLASSIFIED DRUG; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE 2; LU AF33241; PDE10A PROTEIN, HUMAN; PDE2A PROTEIN, HUMAN; PHOSPHODIESTERASE INHIBITOR; QUINOXALINE DERIVATIVE; TRIAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIPSYCHOTIC ACTIVITY; ARTICLE; ATTENTION DEFICIT DISORDER; AVOIDANCE BEHAVIOR; CATALEPSY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG DETERMINATION; DRUG EFFECT; DRUG MECHANISM; DRUG PENETRATION; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME INHIBITION; EXPLORATORY BEHAVIOR; IN VITRO STUDY; IN VIVO STUDY; MALE; MOTOR ACTIVITY; NONHUMAN; NOVEL OBJECT RECOGNITION TEST; PRIORITY JOURNAL; RAT; RECOGNITION; ANIMAL; ANIMAL BEHAVIOR; ANTAGONISTS AND INHIBITORS; BLOOD BRAIN BARRIER; CAPILLARY PERMEABILITY; CHEMICALLY INDUCED; COGNITION; DRUG EFFECTS; HUMAN; METABOLISM; SPRAGUE DAWLEY RAT; WISTAR RAT;

ANIMALS; ANTIPSYCHOTIC AGENTS; AVOIDANCE LEARNING; BEHAVIOR, ANIMAL; BLOOD-BRAIN BARRIER; CAPILLARY PERMEABILITY; CATALEPSY; COGNITION; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 2; EXPLORATORY BEHAVIOR; HUMANS; MALE; MOTOR ACTIVITY; PHOSPHODIESTERASE INHIBITORS; PHOSPHORIC DIESTER HYDROLASES; QUINOXALINES; RATS, SPRAGUE-DAWLEY; RATS, WISTAR; RECOGNITION (PSYCHOLOGY); TRIAZOLES;

EID: 84929168257     PISSN: 00142999     EISSN: 18790712     Source Type: Journal    
DOI: 10.1016/j.ejphar.2015.04.040     Document Type: Article

References (46)

1. A. Aleman, R. Hijman, E.H. de Haan, and R.S. Kahn Memory impairment in schizophrenia: a meta-analysis Am. J. Psychiatry 156 1999 1358 1366
2. J.I. Andrés, P. Buijnsters, M. De Angelis, X. Langlois, F. Rombouts, A.A. Trabanco, and G. Vanhoof Discovery of a new series of [1,2,4]triazolo[4,3-a]quinoxalines as dual phosphodiesterase 2/phosphodiesterase 10 (PDE2/PDE10) inhibitors Bioorg. Med. Chem. Lett. 23 2013 785 790
3. A.T. Bender, and J.A. Beavo Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use Pharmacol. Rev. 58 2006 488 520
4. A Blokland, R Schreiber, and J. Prickaerts Improving memory: a role for phosphodiesterases Curr. Pharm. Des. 12 2006 2511 2523
5. F.G. Boess, M. Hendrix, F.J. van der Staay, C. Erb, R. Schreiber, W. van Staveren, J. de Vente, J. Prickaerts, A. Blokland, and G. Koenig Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance Neuropharmacology 47 2004 1081 1092
6. G.B. Bolger, L. Rodgers, and M. Riggs Differential CNS expression of alternative mRNA isoforms of the mammalian genes encoding cAMP-specific phosphodiesterases Gene 149 1994 237 244
7. L. Clare, P.J. McKenna, A.M. Mortimer, and A.D. Baddeley Memory in schizophrenia: what is impaired and what is preserved? Neuropsychologia 31 1993 1225 1241
8. R.E. Clark, S.M. Zola, and L.R. Squire Impaired recognition memory in rats after damage to the hippocampus J. Neurosci. 20 2000 8853 8860
9. S. Das, D.E. Shelke, R.L. Harde, V.B. Avhad, N. Khairatkar-Joshi, S. Gullapalli, P.K. Gupta, M.N. Gandhi, D.K. Bhateja, M. Bajpai, A.A. Joshi, M.Y. Marathe, G.S. Gudi, S.B. Jadhav, M.Y. Mahat, and A. Thomas Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene ethers as PDE10A inhibitors: Part II Bioorg. Med. Chem. Lett. 24 2014 3238 3242
10. DeMartinis, N., Banerjee, A., Kumar, V., Boyer, S., Schmidt, C.J., Arrojo, S. 2012. Results of a Phase 2A Proof-of-Concept Trial with a PDE10A Inhibitor in the Treatment of Acute Exacerbation of Schizophrenia. Poster 212, Presented at the Society for Biological Psychiatry 2012 Annual Meeting. Philadelphia, PA.
11. A. Ennaceur, and J. Delacour A new one-trial test for neurobiological studies of memory in rats. 1: behavioural data Behav. Brain Res. 31 1988 47 59
12. J. Gerlach New antipsychotics: classification, efficacy, and adverse effects Schizophr. Bull. 17 1991 289 309
13. P.H. Gobira, J. Ropke, D.C. Aguiar, J.A. Crippa, and F.A. Moreira Animal models for predicting the efficacy and side effects of antipsychotic drugs Rev. Bras. Psiquiatr. 35 Suppl 2 2013 S132 S139
14. L. Gomez, and J.G. Breitenbucher PDE2 inhibition: potential for the treatment of cognitive disorders Bioorg. Med. Chem. Lett. 23 2013 6522 6527
15. S.M. Grauer, V.L. Pulito, R.L. Navarra, M.P. Kelly, C. Kelley, R. Graf, B. Langen, S. Logue, J. Brennan, L. Jiang, E. Charych, U. Egerland, F. Liu, K.L. Marquis, M. Malamas, T. Hage, T.A. Comery, and N.J. Brandon Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia J. Pharmacol. Exp. Ther. 331 2009 574 590
16. M Hammarlund-Udenaes Active-site concentrations of chemicals - are they a better predictor of effect than plasma/organ/tissue concentrations? Basic Clin. Pharmacol. Toxicol. 106 2010 215 220
17. A.L. Hebb, H.A. Robertson, and E.M. Denovan-Wright Phosphodiesterase 10A inhibition is associated with locomotor and cognitive deficits and increased anxiety in mice Eur. Neuropsychopharmacol. 18 2008 339 363
18. S. Heckers, T. Curran, D. Goff, S.L. Rauch, A.J. Fischman, N.M. Alpert, and D.L. Schacter Abnormalities in the thalamus and prefrontal cortex during episodic object recognition in schizophrenia Biol. Psychiatry 48 2000 651 657
19. D.C. Hoffman, and H. Donovan Catalepsy as a rodent model for detecting antipsychotic drugs with extrapyramidal side effect liability Psychopharmacology 120 1995 128 133
20. J.D. Jentsch, and R.H. Roth The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia Neuropsychopharmacology 20 1999 201 225
21. Jørgensen, M., Bruun, A.T., Rasmussen, L.K., Larsen, M, 2013. Preparation of substitued triazolopyrazines as PDE2A and PDE10A inhibitors useful for treating neurological and psychiatric disorders. From PCT Int. Appl. WO20130334755 A1 20130314.
22. M.P. Kelly, and N.J. Brandon Differential function of phosphodiesterase families in the brain: gaining insights through the use of genetically modified animals Prog. Brain Res. 179 2009 67 73
23. V. Lakics, E.H. Karran, and F.G. Boess Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues Neuropharmacology 59 2010 367 374
24. J.R. Manns, C.E.L. Stark, and L.R. Squire The visual paired-comparison task as a measure of declarative memory Proc. Natl. Acad. Sci. USA 97 2000 12375 12379
25. J.P. Redrobe, S. Bull, and N. Plath Translational aspects of the novel object recognition task in rats abstinent following sub-chronic treatment with phencyclidine (PCP): effects of modafinil and relevance to cognitive deficits in schizophrenia Front. Psychiatry 1 2010 146
26. J.P. Redrobe, L. Elster, K. Frederiksen, C. Bundgaard, I.E. de Jong, G.P. Smith, A.T. Bruun, P.H. Larsen, and M. Didriksen Negative modulation of GABAA α5 receptors by RO4938581 attenuates discrete sub-chronic and early postnatal phencyclidine (PCP)-induced cognitive deficits in rats Psychopharmacology 221 2012 451 468
27. J.P. Redrobe, M. Jørgensen, C.T. Christoffersen, L.P. Montezinho, J.F. Bastlund, M. Carnerup, C. Bundgaard, L. Lerdrup, and N. Plath In vitro and in vivo characterisation of Lu AF64280, a novel, brain penetrant phosphodiesterase (PDE) 2A inhibitor: potential relevance to cognitive deficits in schizophrenia Psychopharmacology 231 2014 3151 3167
28. O.A. Reneerkens, K. Rutten, E. Bollen, T. Hage, A. Blokland, H.W. Steinbusch, and J. Prickaerts Inhibition of phoshodiesterase type 2 or type 10 reverses object memory deficits induced by scopolamine or MK-801 Behav. Brain Res. 236 2013 16 22
29. D.R. Repaske, J.V. Swinnen, S.L. Jin, J.J. Van Wyk, and M. Conti A polymerase chain reaction strategy to identify and clone cyclic nucleotide phosphodiesterase cDNAs. Molecular cloning of the cDNA encoding the 63-kDa calmodulin-dependent phosphodiesterase J. Biol. Chem. 267 1992 18683 18688
30. E. Reyes-Irisarri, M. Markerink-Van Ittersum, G. Mengod, and J. de Vente Expression of the cGMP-specific phosphodiesterases 2 and 9 in normal and Alzheimer's disease human brains Eur. J. Neurosci. 25 2007 3332 3338
31. J.S. Rodefer, E.R. Murphy, and M.G. Baxter PDE10A inhibition reverses PCP-induced deficits in attentional set-shifting in rats Eur. J. Neurosci. 21 2005 1070 1076
32. P.R. Sanberg, M.D. Bunsey, M. Giordano, and A.B. Norman The catalepsy test: its ups and downs Behav. Neurosci. 102 1988 748 759
33. H. Sano, Y. Nagai, T. Miyakawa, R. Shigemoto, and M. Yokoi Increased social interaction in mice deficient of the striatal medium spiny neuron-specific phosphodiesterase 10A2 J. Neurochem. 105 2008 546 556
34. T.F. Seeger, B. Bartlett, T.M. Coskran, J.S. Culp, L.C. James, D.L. Krull, J. Lanfear, A.M. Ryan, C.J. Schmidt, C.A. Strick, A.H. Varghese, R.D. Williams, P.G. Wylie, and F.S. Menniti Immunohistochemical localization of PDE10A in the rat brain Brain Res. 985 2003 113 126
35. J,A. Siuciak, S.A. McCarthy, D.S. Chapin, R.A. Fujiwara, L.C. James, R.D. Williams, J.L. Stock, J.D. McNeish, C.A. Strick, F.S. Menniti, and C.J. Schmidt Genetic deletion of the striatum-enriched phosphodiesterase PDE10A: evidence for altered striatal function Neuropharmacology 51 2006 374 385
36. J.A. Siuciak, S.A. McCarthy, D.S. Chapin, A.N. Martin, J.F. Harms, and C.J. Schmidt Behavioral characterization of mice deficient in the phosphodiesterase-10A (PDE10A) enzyme on a C57/Bl6N congenic background Neuropharmacology 54 2008 417 427
37. D.A. Smith, L. Di, and E.H. Kerns The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery Nat. Rev. Drug Discov. 9 2010 929 939
38. S.M. Smith, J.M. Uslaner, C.D. Cox, S.L. Huszar, C.E. Cannon, J.D. Vardigan, D. Eddins, D.M. Toolan, M. Kandebo, L. Yao, I.T. Raheem, J.D. Schreier, M.J. Breslin, P.J. Coleman, and J.J. Renger The novel phosphodiesterase 10A inhibitor THPP-1 has antipsychotic-like effects in rat and improves cognition in rat and rhesus monkey Neuropharmacology 64 2013 215 223
39. F. Sotty, T. Damgaard, L.P. Montezinho, A. Mørk, C.K. Olsen, C. Bundgaard, and H. Husum Antipsychotic-like effect of retigabine [N-(2-Amino-4-(fluorobenzylamino)-phenyl)carbamic acid ester], a KCNQ potassium channel opener, via modulation of mesolimbic dopaminergic neurotransmission J. Pharmacol. Exp. Ther. 328 2009 951 962
40. D.T. Stephenson, T.M. Coskran, M.B. Wilhelms, W.O. Adamowicz, M.M. O'Donnell, K.B. Muravnick, F.S. Menniti, R.J. Kleiman, and D. Morton Immunohistochemical localization of phosphodiesterase 2A in multiple mammalian species J. Histochem. Cytochem. 57 2009 933 949
41. D.T. Stephenson, T.M. Coskran, M.P. Kelly, R.J. Kleiman, D. Morton, S.M. O'Neill, C.J. Schmidt, R.J. Weinberg, and F.S. Menniti The distribution of phosphodiesterase 2A in the rat brain Neuroscience 226 2012 145 155
42. C. Tek, J. Gold, T. Blaxton, C. Wilk, R.P. McMahon, and R.W. Buchanan Visual perceptual and working memory impairments in schizophrenia Arch. Gen. Psychiatry 59 2002 146 153
43. E.L. van Donkelaar, K. Rutten, A. Blokland, S. Akkerman, H.W. Steinbusch, and J. Prickaerts Phosphodiesterase 2 and 5 inhibition attenuates the object memory deficit induced by acute tryptophan depletion Eur. J. Pharmacol. 600 2008 98 104
44. W.C. van Staveren, H.W. Steinbusch, M. Markerink-Van Ittersum, D.R. Repaske, M.F. Goy, J. Kotera, K. Omori, J.A. Beavo, and J. De Vente mRNA expression patterns of the cGMP-hydrolyzing phosphodiesterases types 2, 5, and 9 during development of the rat brain J. Comp. Neurol. 467 2003 566 580
45. M.L. Wadenberg Conditioned avoidance response in the development of new antipsychotics Curr. Pharm. Des. 16 2010 358 370
46. J.W. Young, S.B. Powell, V. Risbrough, H.M. Marston, and M.A. Geyer Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia Pharmacol. Ther. 122 2009 150 202