Novel NK3 receptor antagonists for the treatment of schizophrenia and other CNS indications

Current Opinion in Drug Discovery and Development

Volumn 13, Issue 4, 2010, Pages 379-388

  Simonsen, Klaus B ^a   Juhl, Karsten ^a   Steiniger Brach, Bjöern ^a   Nielsen, Søren Møller ^a  

^a H LUNDBECK A S   (Denmark)

Author keywords

Neurokinin b; neuropsychiatric disorder; Nk 3 receptor antagonist; Nk3 receptor; osanetant; peptide receptor; schizophrenia; tachykinin; talnetant

Indexed keywords

AZD 2624; EPLIVANSERIN; HALOPERIDOL; MAMMALIAN TACHYKININ RECEPTOR 3; MECLINERTANT; NEUROTENSIN RECEPTOR ANTAGONIST; OLANZAPINE; OSANETANT; PAROXETINE; PROLACTIN; RIMONABANT; RISPERIDONE; SENKTIDE; TACHYKININ RECEPTOR ANTAGONIST; TALNETANT; TETRAGASTRIN; UNCLASSIFIED DRUG; NEUROKININ 3 RECEPTOR; NEUROLEPTIC AGENT;

ASTHMA; CENTRAL NERVOUS SYSTEM; CHRONIC LUNG DISEASE; COUGHING; DNA TEMPLATE; DRUG EFFICACY; DRUG INDICATION; DRUG TOLERANCE; HUMAN; IRRITABLE COLON; MAJOR DEPRESSION; METHODOLOGY; NONHUMAN; PAIN; PANIC; PARKINSON DISEASE; REVIEW; SCHIZOPHRENIA; SINGLE DRUG DOSE; UNSPECIFIED SIDE EFFECT; URINE INCONTINENCE; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG EFFECTS; GENETICS; METABOLISM; PATHOLOGY;

ANIMALS; ANTIPSYCHOTIC AGENTS; CENTRAL NERVOUS SYSTEM; HUMANS; RECEPTORS, NEUROKININ-3; SCHIZOPHRENIA;

EID: 77954647865     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (77)

1. Hastrup H, Schwartz TW: Septide and neurokinin A are highaffinity ligands on the NK1 receptor: Evidence from homologous versus heterologous binding analysis. FEBS Lett (1996)399(3):264-266.
2. Maggi CA: The mammalian tachykinin receptors. Gen Pharmacol (1995)26(5):911-944.
3. Beaujouan JC, Torrens Y, Saffroy M, Kernel ML, Glowinski J: A 25 year adventure in the field of tachykinins. Peptides (2004)25(3):339-357.
4. Langlois X, Wintmolders C, te Riele P, Leysen JE, Jurzak M: Detailed distribution of neurokinin 3 receptors in the rat, guinea pig and gerbil brain: A comparative autoradiographic study. Neuropharmacology (2001)40(2):242-253.
5. 1) receptor predominates in human brain. J Comp Neurol (2005)490(4):335-353.
6. Almeida TA, Rojo J, Nieto PM, Pinto FM, Hernandez M, Martin JD, Candenas ML: Tachykinins and tachykinin receptors: Structure and activity relationships. Curr Med Chem (2004)11(15):2045-2081. (Pubitemid 38967729)
7. 3 receptor as reduces involved in species-selective binding to SR 48968. Biochem Biophys Res Commun (1994)198(3):961-966.
8. Stoessl AJ: Localization of striatal and nigral tachykinin receptors in the rat. Brain Res (1994)646(1):13-18.
9. Furuta T, Kaneko T: Third pathway in the cortico-basal ganglia loop: Neurokinin B-producing striatal neurons modulate cortical activity via striato-innominato-cortical projection. Neurosci Res (2006)54(1):1-10.
10. 3 receptor stimulation in gerbil mesencephalic cell cultures. Eur J Neurosci (1996)8(4):1801-808.
11. 3 receptor stimulation. Neuroscience (1996)74(2):403-414.
12. Nalivaiko E, Michaud JC, Soubrie P, Lefur G, Feltz P: Tachykinin neurokinin-1 and neurokinin-3 receptor-mediated responses in guinea-pig substantia nigra: An in vitro electrophysiological study. Neuroscience (1997)78(3):745-757.
13. 1 receptor-mediated activation of the locus coeruleus revealed by SR 142801. Synapse (2002)43(1):62-69.
14. Stoessl AJ, Szczutkowski E, Glenn B, Watson I: Behavioural effects of selective tachykinin agonists in midbrain dopamine regions. Brain Res (1991)565(2):254-262.
15. Bannon MJ, Brownschidle LA, Tian Y, Whitty CJ, Poosch MS, D'sa C, Moody CA: Neurokinin-3 receptors modulate dopamine cell function and alter the effects of 6-hydroxydopamine. Brain Res (1995)695(1):19-24.
16. Arenas E, Alberch J, Pereznavarro E, Solsona C, Marsal J: Neurokinin receptors differentially mediate endogenous acetylcholine release evoked by tachykinins in the neostriatum. J Neurosci (1991)11(8):2332-2338.
17. 3H]acetylcholine release in mouse striatum through multiple receptor subtypes. Neuroscience (2000)95(2):367-376.
18. Furuta T, Koyano K, Tomioka R, Yanagawa Y, Kaneko T: GABAergic basal forebrain neurons that express receptor for neurokinin B and send axons to the cerebral cortex. J Comp Neurol (2004)473(1):43-58.
19. Liu RJ, Ding YQ, Aghajanian GK: Neurokinins activate local glutamatergic inputs to serotonergic neurons of the dorsal raphe nucleus. Neuropsychopharmacology (2002)27(3):329-340.
20. Stacey AE, Woodhall GL, Jones RS: Neurokinin-receptor-mediated depolarization of cortical neurons elicits an increase in glutamate release at excitatory synapses. Eur J Neurosci (2002)16(10):1896-1906.
21. 3 receptor activation depolarizes and induces an after-depolarization in pyramidal neurons in gerbil cingulate cortex. Brain Res Bull (2004)63(2):85-90.
22. Nordquist RE, Savignac H, Pauly-Evers M, Walker G, Knoflach F, Borroni E, Glaentzlin P, Bohrmann B, Messer J, Ozmen L, Albientz A et al: Characterization of behavioral response to amphetamine, tyrosine hydroxylase levels, and dopamine receptor levels in neurokinin 3 receptor knockout mice. Behav Pharmacol (2008)19(5-6):518-529.
23. Nordquist RE, Delenclos M, Ballard TM, Savignac H, Pauly-Evers M, Ozmen L, Spooren W: Cognitive performance in neurokinin 3 receptor knockout mice. Psychopharmacology (2008)198(2):211-220.
24. 3) in mice leads to cognitive deficits. Psychopharmacology (2007)194(2):185-195.
25. Mesnage V, Houeto JL, Bonnet AM, Clavier I, Arnulf I, Cattelin F, Le Fur G, Damier P, Welter ML, Agid Y: Neurokinin B, neurotensin, and cannabinoid receptor antagonists and Parkinson disease. Clin Neuropharmacol (2004)27(3):108-110.
26. Meltzer HY, Arvanitis L, Bauer D, Rein W: Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am J Psychiatry (2004)161(6):975-984. •• Describes the results of the first clinical trial of osanetant in patients with schizophrenia, in which osanetant demonstrated significant effects on PANSS and CGI scores.
27. Information meeting on full year 2002 results. Sanofi-Synthélabo Company Presentation (2003).
28. 3) receptor antagonist in panic disorder with pre- and posttreatment cholecystokinin tetrapeptide (CCK4) challenges. Pharmacopsychiatry (2005)38(1):24-29.
29. Evangelista S: Talnetant (GlaxoSmithKline). Curr Opin Investig Drugs (2005)6(7):717-721.
30. 3) receptor modulators for the treatment of psychiatric disorders. Recent Pat CNS Drug Discov (2008)3(1):1-15.
31. 3 receptor antagonists for the treatment of schizophrenia and other neuropsychiatric disorders.
32. 3 receptor antagonists for the treatment of schizophrenia. Drug Disc Today (2006)3(4):555-560.
33. 3 system.
34. 3 receptor stimulation: An in vivo microdialysis approach in guinea pig. Neuropeptides (1998)32(5):481-488.
35. 3 receptor antagonist SB-223412 (talnetant): Potential therapeutic utility in the treatment of schizophrenia. Neuropsychopharmacology (2008)33(7):1642-1652. • Describes the preclinical mode of action of talnetant, which modulates mesolimbic and mesocortical dopaminergic neurotransmission.
36. 3 receptor antagonists for the treatment of schizophrenia. Society of Neuroscience Annual Meeting, San Diego, CA, USA (2007) 33: Abs 500.10.
37. 3 receptor antagonist talnetant (SB-223412). Neuropharmacology (2009)56(2):342-349.
38. sanofi-aventis: sanofi-aventis announces strong growth in 2005. Press Release (2005): August 31.
39. GSK psychiatry pipeline update: 353162, 597599, talnetant and 468816. GlaxoSmithKline plc Company Presentation (2003): December 03.
40. GSK psychiatry pipeline update: 597599, 372475, 649868 and talnetant. GlaxoSmithKline plc Company Presentation (2004): November 23.
41. 3 hypothesis in schizophrenia. American Chemical Society National Meeting, San Francisco, CA, USA (2010) 239: Abs MEDI 35.
42. Stoessl AJ, Dourish CT, Young SC, Williams BJ, Iversen SD, Iversen LL: Senktide, a selective neurokinin B-like agonist, elicits serotonin-mediated behaviour following intracisternal administration in the mouse. Neurosci Lett (1987)80(3):321-326.
43. 3 tachykinin receptor agonist senktide elicits 5-HT-mediated behaviour following central or peripheral administration in mice and rats. Br J Pharmacol (1988)94(2):285-287.
44. Dableh LJ, Yashpal K, Rochford J, Henry JL: Antidepressantlike effects of neurokinin receptor antagonists in the forced swim test in the rat. Eur J Pharmacol (2005)507(1-3):99-105.
45. 3 receptors produces anxiolytic- and antidepressant-like effects in gerbils. Pharmacol Biochem Behav (2006)83(4):533-539.
46. 3 receptor involvement in anxiety. Neuropeptides (1999)33(2):181-188.
47. 3 tachykinin receptor agonist aminosenktide in mouse lines differing in endogenous opioid system activity. Peptides (2001)22(7):1037-1042.
48. Chen JJ: Anxiety, depression, and psychosis in Parkinson's disease: Unmet needs and treatment challenges. Neurol Clin (2004)22(3 Suppl):S63-S90.
49. Brotchie JM: Adjuncts to dopamine replacement: A pragmatic approach to reducing the problem of dyskinesia in Parkinson's disease. Mov Disord (1998)13(6):871-876.
50. Albert JS, Potts W: Neurokinin-3 receptor antagonists in schizophrenia. Expert Opin Ther Pat (2006)16(7):925-937.
51. Giardina GA, Raveglia LF, Grugni M, Sarau HM, Farina C, Medhurst AD, Graziani D, Schmidt DB, Rigolio R, Luttmann M, Cavagnera S et al: Discovery of a novel class of selective non-peptide antagonists for the human neurokinin-3 receptor. 2. Identification of (S)-N-(1-phenylpropyl)-3-hydroxy-2- phenylquinoline-4-carboxamide (SB 223412). J Med Chem (1999)42(6):1053-1065.
52. Alvaro G, Di Fabio R: Neurokinin 1 receptor antagonists - Current prospects. Curr Opin Drug Discov Dev (2007)10(5):613-621.
53. Janssen Pharmaceutica NV [Johnson & Johnson] (Janssens FE, Sommen FM, De Boeck BCAG, Leenaerts JE): Substituted 1-piperidin-4-yl-4-azetidin-3-yl- piperazine derivatives and their use as neurokinin antagonists. WO-2004056800 (2004).
54. Janssen Pharmaceutica NV [Johnson & Johnson] (Janssens FE, Sommen FM, De Boeck BCAG, Leenaerts JE): Substituted 4-(4-piperidin-4-yl-piperazin-1-yl)- azepane derivatives and their use as neurokinin antagonists. WO-2004056805 (2004).
55. 2, receptor antagonists.
56. 3 receptor antagonists with CNS activity. Bioorg Med Chem Lett (2009)19(3):837-840. •• Presents ex vivo binding studies with osanetant, talnetant, and compounds 3 and 4. The free brain concentrations of the four compounds were also measured.
57. Elliott JM, Carling RW, Chambers M, Chicchi GG, Hutson PH, Jones AB, MacLeod A, Marwood R, Meneses-Lorente G, Mezzogori E, Murray F et al: N', 2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists. Bioorg Med Chem Lett (2006)16(22):5748-5751.
58. 3 receptor antagonists II. Bioorg Med Chem Lett (2006)16(22):5752-5756.
59. AstraZeneca AB (Simpson TR, Kang J, Albert JS, Alhambra C, Koether GM, Woods J, Li Y): Quinoline 3-sulfonate esters as NK3 receptor modulators. WO-2006137789 (2006).
60. AstraZeneca AB (Simpson T, Kang J, Albert J, Alhambra C, Koether G, Woods J, Li Y): Alkylsulphonamide quinolines. WO-2007069977 (2007).
61. 3 receptor ligands. WO-2007035158 (2007).
62. AstraZeneca AB (Kang J, McCauley JP, Simpson TR): Quinoline derivatives, pharmaceutical compositions comprising them, and their use in treating central nervous system and peripheral diseases. WO-2008115140 (2008).
63. 3 antagonists. WO-2008131779 (2008).
64. 3 antagonists. WO-2009156339 (2009).
65. 3 receptor antagonists. WO-2005016884 (2005).
66. F Hoffmann-La Roche Ltd (Knust H, Nettekoven M, Ratni H, Wu X): Piperazine and [1, 4] diazepan derivatives as NK antagonists. WO-2008151969 (2008).
67. 3 receptor antagonists. WO-2009033995 (2009).
68. 3 antagonists. WO-2008148689 (2008).
69. 3 receptor antagonists. WO-2008148688 (2008).
70. 3 receptor antagonists. WO-2009019163 (2009).
71. 3 receptor antagonists. WO-2009024502 (2009).
72. 3 antagonists against schizophrenia. WO-2006013050 (2006).
73. 3 antagonists for treating schizophrenia. WO-2005002577 (2005).
74. 1 receptor antagonism: A novel approach for the treatment of psychotic disorders. New Drugs and Drug Candidates: Recent Achievements in Medicinal Chemistry, UCB, Braine-l'Alleud, Belgium (2007).
75. Neurogen Corp (Maynard G, Rachwal S, Pringle W, Yuan J, Xie L, Xu Y, Han B): 2, 5-Diaryl-1H-imidazole-4-carboxamides as neurokinin-3 receptor modulators for the treatment of central nervous system and peripheral diseases. WO-2002066137 (2005).
76. Neurogen Corp (Maynard GD, Yuan J, Peterson JM): Neurokinin-3 receptor modulators: Diaryl pyrazole derivatives. WO-2005061462 (2005).
77. Hitchcock SA, Pennington LD: Structure-brain exposure relationships. J Med Chem (2006)49(26):7559-7583.