Targeting of α7 nicotinic acetylcholine receptors in the treatment of schizophrenia and the use of auditory sensory gating as a translational biomarker

Current Pharmaceutical Design

Volumn 21, Issue 26, 2015, Pages 3797-3806

  Hashimoto, Kenji ^a  

^a CHIBA UNIVERSITY   (Japan)

Author keywords

Agonists; Allosteric positive modulators; Auditory sensory gating; Biomarker; Schizophrenia; 7 nicotinic acetylcholine receptors

Indexed keywords

1 AZABICYCLO[2.2.2]OCT 3 YL] 1H INDAZOLE 3 CARBOXAMIDE; 3 (2,4 DIMETHOXYBENZYLIDENE)ANABASEINE; 3 (6 4 TOLYL PYRIDIN 3 YLOXY) 1 AZA BICYCLO[2.2.2.]OCTANE; 4 [(5 PHENYL 1,3,4 THIADIAZOL 2 YL)OXY] 1 AZONIATRICYCLO[3.3.1.1 3,7]DECANE 3,4 DICARBOXY 3 HYDROXYBUTANOATE; BRADANICLINE; BUNGAROTOXIN RECEPTOR; ENCENICLINE; JNJ 39393406; N (4 CHLOROPHENYL) ALPHA [[(4 CHLOROPHENYL)AMINO]METHYLENE] 3 METHYL 5 ISOXAZOLEACE; NEUROLEPTIC AGENT; NICOTINIC AGENT; TROPISETRON; UNCLASSIFIED DRUG; 3-(2,4-DIMETHOXYBENZYLIDENE)ANABASEINE; BENZYLIDENE DERIVATIVE; BIOLOGICAL MARKER; PYRIDINE DERIVATIVE;

ARTICLE; AUDITORY SENSORY GATING; BRAIN LEVEL; CHOLINERGIC STIMULATION; CINGULATE GYRUS; COGNITIVE DEFECT; DENTATE GYRUS; DISEASE ASSOCIATION; DRUG EFFECT; DRUG EFFICACY; DRUG TARGETING; EVOKED AUDITORY RESPONSE; FRONTAL GYRUS; HIPPOCAMPAL CA3 REGION; HUMAN; MULTICENTER STUDY (TOPIC); NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECEPTOR DENSITY; SCHIZOPHRENIA; SENSORY GATING; THALAMUS RETICULAR NUCLEUS; AGONISTS; ANIMAL; AUDITORY EVOKED POTENTIAL; DRUG EFFECTS; PATHOPHYSIOLOGY; PHYSIOLOGY;

ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR; ANIMALS; ANTIPSYCHOTIC AGENTS; BENZYLIDENE COMPOUNDS; BIOMARKERS; EVOKED POTENTIALS, AUDITORY; HUMANS; PYRIDINES; SCHIZOPHRENIA; SENSORY GATING;

EID: 84942133427     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612821666150605111345     Document Type: Article

References (153)

1. Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, Bor DH. Smoking and mental illness: A population-based prevalence study. JAMA 2000; 284: 2606-10.
2. Uck A, Polat A, Bozkurt O, Meteris H. Cigarette smoking among patients with schizophrenia and bipolar disorders. Psychiatr Clin Neurosci 2004; 58: 434-7.
3. de Leon J, Diaz FJ. A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophr Res 2005; 76: 135-57.
4. Aubin HJ, Rollema H, Svensson TH, Winterer G. Smoking, quitting, and psychiatric disease: a review. Neurosci Biobehav Rev 2012; 36: 271-84.
5. Tsoi DT, Porwal M, Webster AC. Interventions for smoking cessation and reduction in individuals with schizophrenia. Cochrane Database Syst Rev 2013; 2: CD007253.
6. Kumari V, Postma P. Nicotine use in schizophrenia: the selfmedication hypotheses. Neurosci Biobehav Rev 2005; 29: 1021-34.
7. Leonard S, Mexal S, Freedman R. Smoking, genetics and schizophrenia: evidence for self medication. J Dual Diagn 2007; 3: 43-59.
8. Goff DC, Henderson DC, Amico E. Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. Am J Psychiatry 1992; 149: 1189-94.
9. Tung CS, Grenhoff J, Svensson TH. Nicotine counteracts midbrain dopamine cell dysfunction induced by prefrontal cortex inactivation. Acta Physiol Scand 1990; 138: 427-8.
10. Glassman AH. Cigarette smoking: implications for psychiatric illness. Am J Psychiatry 1993; 150: 546-53.
11. Nisell M, Nomikos GG, Svensson TH. Nicotine dependence, midbrain dopamine systems and psychiatric disorders. Pharmacol Toxicol 1995; 76: 157-62.
12. Dani JA, Bertrand D. Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu Rev Pharmacol Toxicol 2007; 47: 699-729.
13. Simosky JK, Stevens KE, Freedman R. Nicotinic agonists and psychosis. Curr Drug Targets CNS Neurol Disord 2002; 1: 149-62.
14. Martin LF, Kem WR, Freedman R. Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia. Psychopharmacology (Berl) 2004; 174: 54-64.
15. Hashimoto K, Koike K, Shimizu E, Iyo M. α7 Nicotinic receptor agonists as potential therapeutic drugs for schizophrenia. Curr Med Chem CNS Agents 2005; 5: 171-84.
16. Olincy A, Stevens KE. Treating schizophrenia symptoms with an α7 nicotinic agonist, from mice to men. Biochem Pharmacol 2007; 74: 1192-201.
17. Hajós M, Rogers BN. Targeting α7 nicotinic acetylcholine receptors in the treatment of schizophrenia. Curr Pharm Des 2010; 16: 538-54.
18. Toyohara J, Hashimoto K. α7 Nicotinic receptor agonists: potential therapeutic drugs for treatment of cognitive impairments in schizophrenia and Alzheimer's disease. Open Med Chem J 2010; 4: 37-56.
19. Thomsen MS, Hansen HH, Timmerman DB, Mikkelsen JD. Cognitive improvement by activation of α7 nicotinic acetylcholine receptors: from animal models to human pathophysiology. Curr Pharm Des 2010; 16: 323-43.
20. Ishikawa M, Hashimoto K. α7 Nicotinic receptor as a potential therapeutic target for schizophrenia. Curr Pham Des 2011; 17: 121-9.
21. Jones CK, Byun N, Bubser M. Muscarinic and nicotinic acetylcholine receptor agonists and allosteric modulators for the treatment of schizophrenia. Neuropsychopharmacology 2012; 37: 16-42.
22. Hurst R, Rollema H, Bertrand D. Nicotinic acetylcholine receptors: from basic science to therapeutics. Pharmacol Ther 2013; 137: 22-54.
23. Young JW, Geyer MA. Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophrenia. Biochem Pharmacol 2013; 86: 1122-32.
24. Adler LE, Pachtman E, Franks RD, Pecevich M, Waldo MC, Freedman R. Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. Biol Psychiatry 1982; 17: 639-54.
25. Freedman R, Adler LE, Waldo MC, Pachtman E, Franks RD. Neurophysiological evidence for a defect in inhibitory pathways in schizophrenia: comparison of medicated and drug-free patients. Biol Psychiatry 1983; 18: 537-51.
26. Freedman R, Adler LE, Gerhardt GA, et al. Neurobiological studies of sensory gating in schizophrenia. Schizophr Bull 1987; 13: 669-78.
27. Judd LL, McAdams L, Budnick B, Braff DL. Sensory gating deficits in schizophrenia: new results. Am J Psychiatry 1992; 149: 488-93.
28. Clementz BA, Geyer MA, Braff DL. P50 suppression among schizophrenia and normal comparison subjects: a methodological analysis. Biol Psychiatry 1997; 41: 1035-44.
29. Siegel C, Waldo M, Mizner G, Adler LE, Freedman R. Deficits in sensory gating in schizophrenic patients and their relatives. Evidence obtained with auditory evoked responses. Arch Gen Psychiatry 1984; 41: 607-12.
30. Waldo MC, Adler LE, Freedman R. Defects in auditory sensory gating and their apparent compensation in relatives of schizophrenics. Schizophr Res 1988; 1: 19-24.
31. Clementz BA, Geyer MA, Braff DL. Poor P50 suppression among schizophrenia patients and their first-degree biological relatives. Am J Psychiatry 1998; 155: 1691-4.
32. Ross RG, Olincy A, Harris JG, et al. Evidence for bilineal inheritance of physiological indicators of risk in childhood-onset schizophrenia. Am J Med Genet 1999; 88: 188-99.
33. Heinrichs RW. Meta-analysis and the sciences of schizophrenia: variant evidence or evidence of variants? Neurosci Biobehav Rev 2004; 28: 379-94.
34. Potter D, Summerfelt A, Gold J, Buchanan RW. Review of clinical correlates of P50 sensory gating abnormalities in patients with schizophrenia. Schizophr Bull 2006; 32: 692-700.
35. Bramon E, Rabe-Hesketh S, Sham P, Murray RM, Frangou S. Meta-analysis of the P300 and P50 waveforms in schizophrenia. Schizophr Res 2004; 70: 315-29.
36. Patterson JV, Hetrick WP, Boutros NN, Jin Y, Sandman C, Potkin S, Bunney WE. P50 sensory gating ratios in schizophrenia and controls: a review and data analysis. Psychiatry Res 2008; 158: 226-47.
37. Brockhaus-Dumke A, Schultze-Lutter F, Mueller R, et al. Sensory gating in schizophrenia: P50 and N100 gating in antipsychotic-free subjects at risk, first-episode, and chronic patients. Biol Psychiatry 2008; 64: 376-84.
38. Hsieh MH, Shan JC, Huang WL, et al. Auditory event-related potential of subjects with suspected pre-psychotic state and firstepisode psychosis. Schizophr Res 2012; 140: 243-9.
39. van Tricht MJ, Nieman DH, Koelman JT, et al. Sensory gating in subjects at ultra high risk for developing a psychosis before and after a first psychotic episode. World J Biol Psychiatry 2015; 16: 12-21.
40. Stevens KE, Freedman R, Collins AC, Hall M, Leonard S. Genetic correlation of inhibitory gating of hippocampal auditory evoked response and α-bungarotoxin-binding nicotinic cholinergic receptors in inbred mouse strains. Neuropsychopharmacology 1996; 15: 152-62
41. Adams CE, Stevens KE. Evidence for a role of nicotinic acetylcholine receptors in schizophrenia. Front Biosci 2007; 12: 4755-72.
42. Singer P, Feldon J, Yee BK. Are DBA/2 mice associated with schizophrenia-like endophenotypes? A behavioural contrast with C57BL/6 mice. Psychopharmacology (Berl) 2009; 206: 677-98.
43. Simosky JK, Stevens KE, Adler LE, Freedman R. Clozapine improves deficient inhibitory auditory processing in DBA/2 mice, via a nicotinic cholinergic mechanism. Psychopharmacology 2003; 165: 386-96.
44. Nagamoto HT, Adler LE, McRae KA, et al. Auditory P50 in schizophrenics on clozapine: improved gating parallels clinical improvement and changes in plasma 3-methoxy-4-hydroxyphenylglycol. Neuropsychobiology 1999; 39: 10-7.
45. Light GA, Geyer MA, Clementz BA, Cadenhead KS, Braff DL. Normal P50 suppression in schizophrenia patients treated with atypical antipsychotic medications. Am J Psychiatry 2000; 157: 767-71.
46. Shirazi-Southall S, Rodriguez DE, Nomikos GG. Effects of typical and atypical antipsychotics and receptor selective compounds on acetylcholine efflux in the hippocampus of the rat. Neuropsychopharmacology 2002; 26: 583-94.
47. Freedman R, Hall M, Adler LE, Leonard S. Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia. Biol Psychiatry 1995; 38: 22-33.
48. Court J, Spurden D, Lloyd S, et al. Neuronal nicotinic receptors in dementia with Lewy bodies and schizophrenia: α-bungarotoxin and nicotine binding in the thalamus. J Neurochem 1999; 73: 1590-7.
49. Guan ZZ, Zhang X, Blennow K, Nordberg A. Decreased protein level of nicotinic receptor α7 subunit in the frontal cortex from schizophrenic brain. Neuroreport 1999; 10: 1779-82.
50. Marutle A, Zhang X, Court J, et al. Laminar distribution of nicotinic receptor subtypes in cortical regions in schizophrenia. J Chem Neuroanat 2001; 22: 115-26.
51. Martin-Ruiz CM, Haroutunian VH, Long P, et al. Dementia rating and nicotinic receptor expression in the prefrontal cortex in schizophrenia. Biol Psychiatry 2003; 54: 1222-33.
52. Freedman R, Ross R, Leonard S, et al. Early biomarkers of psychosis. Dialog Clin Neurosci 2005; 7: 17-29.
53. Adler LE, Hoffer LD, Wiser A, Freedman R. Normalization of auditory physiology by cigarette smoking in schizophrenic patients. Am J Psychiatry 1993; 150: 1856-61.
54. Adler LE, Hoffer LJ, Griffith J, Waldo MC, Freedman R. Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics. Biol Psychiatry 1992; 32: 607-16.
55. Radek RJ, Miner HM, Bratcher NA, Decker MW, Gopalakrishnan M, Bitner RS. α4β2 nicotinic receptor stimulation contributes to the effects of nicotine in the DBA/2 mouse model of sensory gating. Psychopharmacology (Berl). 2006; 187: 47-55.
56. Freedman R, Adler LE, Bickford P, et al. Schizophrenia and nicotinic receptors. Harv Rev Psychiatry 1994; 2: 179-92.
57. Olincy A, Freedman R. Nicotinic mechanisms in the treatment of psychiatric disorders: a focus on the α7 nicotinic receptor. Handb Exp Pharmacol 2012; 213: 211-32.
58. Freedman R, Coon H, Myles-Worsley M, et al. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci USA 1997; 94: 587-92.
59. Leonard S, Gault J, Moore T, et al. Further investigation of a chromosome 15 locus in schizophrenia: analysis of affected sibpairs from the NIMH Genetics Initiative. Am J Med Genet 1998; 81: 308-12.
60. Neves-Pereira M, Bassett AS, Honer WG, Lang D, King NA, Kennedy JL. No evidence for linkage of the CHRNA7 gene region in Canadian schizophrenia families. Am J Med Genet 1998; 81: 361-3.
61. Curtis L, Blouin JL, Radhakrishna U, et al. No evidence for linkage between schizophrenia and markers at chromosome 15q13-14. Am J Med Genet 1999; 88: 109-12.
62. Leonard S, Gault J, Hopkins J, et al. Association of promoter variants in the α7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia. Arch Gen Psychiatry 2002; 59: 1085-96.
63. Leonard S, Freedman R. Genetics of chromosome 15q13-q14 in schizophrenia. Biol Psychiatry 2006; 60: 115-22.
64. Olincy A, Braff DL, Adler LE, et al. Inhibition of the P50 cerebral evoked response to repeated auditory stimuli: results from the Consortium on Genetics of Schizophrenia. Schizophr Res 2010; 119: 175-82.
65. Greenwood TA, Lazzeroni LC, Murray SS, et al. Analysis of 94 candidate genes and 12 endophenotypes for schizophrenia from the Consortium on the Genetics of Schizophrenia. Am J Psychiatry 2011; 168: 930-46.
66. Gault J, Robinson M, Berger R, et al. Genomic organization and partial duplication of the human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7). Genomics 1998; 52: 173-85.
67. Araud T, Graw S, Berger R, et al. The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7 nAchR function. Biochem Pharmacol 2011; 82: 904-14.
68. Sinkus ML, Lee MJ, Gault J, et al. A 2-base pair deletion polymorphism in the partial duplication of the α7 nicotinic acetylcholine gene (CHRFAM7A) on chromosome 15q14 is associated with schizophrenia. Brain Res 2009; 129: 1-11.
69. Wishka DG, Walker DP, Yates KM, et al. Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2, 3-c]pyridine-5-carboxamide, an agonist of the α7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: synthesis and structure--activity relationship. J Med Chem 2006; 49: 4425-36.
70. Walker DP, Wishka DG, Piotrowski DW, et al. Design, synthesis, structure-activity relationship, and in vivo activity of azabicyclic aryl amides as α7 nicotinic acetylcholine receptor agonists. Bioorg Med Chem 2006; 14: 8219-48.
71. Malysz J, Anderson DJ, Grønlien JH, et al. In vitro pharmacological characterization of a novel selective α7 neuronal nicotinic acetylcholine receptor agonist ABT-107. J Pharmacol Exp Ther 2010; 334: 863-74.
72. Bitner RS, Bunnelle WH, Decker MW, et al. In vivo pharmacological characterization of a novel selective α7 neuronal nicotinic acetylcholine receptor agonist ABT-107: preclinical considerations in Alzheimer's disease. J Pharmacol Exp Ther 2010; 334: 875-86.
73. Othman AA, Lenz RA, Zhang J, et al. Single-and multiple-dose pharmacokinetics, safety, and tolerability of the selective α7 neuronal nicotinic receptor agonist, ABT-107, in healthy human volunteers. J Clin Pharmacol 2011; 51: 512-26.
74. Biton B, Bergis OE, Galli F, et al. SSR180711, a novel selective alpha7 nicotinic receptor partial agonist: (1) binding and functional profile. Neuropsychopharmacology 2007; 32: 1-16.
75. Pichat P, Bergis OE, Terranova JP, et al. SSR180711, a novel selective α7 nicotinic receptor partial agonist: (II) efficacy in experimental models predictive of activity against cognitive symptoms of schizophrenia. Neuropsychopharmacology 2007; 32: 17-34.
76. Hashimoto K, Ishima T, Fujita Y, et al. Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the novel selective α7 nicotinic receptor agonist SSR180711. Biol Psychiatry 2008; 63: 92-7.
77. O'Donnell CJ, Rogers BN, Bronk BS, et al. Discovery of 4-(5-methyloxazolo[4, 5-b]pyridin-2-yl)-1, 4-diazabicyclo[3.2.2]nonane (CP-810, 123), a novel α7 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders in schizophrenia: synthesis, SAR development, and in vivo efficacy in cognition models. J Med Chem 2010; 53: 1222-37.
78. Sydserff S, Sutton EJ, Song D, et al. Selective α7 nicotinic receptor activation by AZD0328 enhances cortical dopamine release and improves learning and attentional processes. Biochem Pharmacol 2009; 78: 880-8.
79. Castner SA, Smagin GN, Piser TM, et al. Immediate and sustained improvements in working memory after selective stimulation of α7 nicotinic acetylcholine receptors. Biol Psychiatry 2011; 69: 12-18.
80. Mazurov AA, Kombo DC, Hauser TA, et al. Discovery of (2S, 3R)-N-[2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3-yl]benzo[b] furan-2-carboxamide (TC-5619), a selective α7 nicotinic acetylcholine receptor agonist, for the treatment of cognitive disorders. J Med Chem 2012; 55: 9793-809.
81. Stevens KE, Kem WR, Mahnir VM, Freedman R. Selective α7-nicotinic agonists normalize inhibition of auditory response in DBA mice. Psychopharmacology (Berl) 1998; 136: 320-7.
82. Simosky JK, Stevens KE, Kem WR, Freedman R. Intragastric DMXB-A, an α7 nicotinic agonist, improves deficient sensory inhibition in DBA/2 mice. Biol Psychiatry 2001; 50: 493-500.
83. Stevens KE, Cornejo B, Adams CE, et al. Continuous administration of a selective α7 nicotinic partial agonist, DMXBA, improves sensory inhibition without causing tachyphylaxis or receptor upregulation in DBA/2 mice. Brain Res 2010; 1352: 140-6.
84. O'Neill HC, Rieger K, Kem WR, Stevens KE. DMXB, an α7 nicotinic agonist, normalizes auditory gating in isolation-reared rats. Psychopharmacology (Berl) 2003; 169: 332-9.
85. Kitagawa H, Takenouchi T, Azuma R, et al. Safety, pharmacokinetics, and effects on cognitive function of multiple doses of GTS-21 in healthy, male volunteers. Neuropsychopharmacology 2003; 28: 542-51.
86. Olincy A, Harris J, Johnson L, et al. Proof of concept trial of an α7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry 2006; 63: 630-8.
87. Freedman R, Olincy A, Buchanan RW, et al. Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am J Psychiatry 2008; 165: 1040-7.
88. Tregellas JR, Olincy A, Johnson L, et al. Functional magnetic resonance imaging of effects of a nicotinic agonist in schizophrenia. Neuropsychopharmacology 2010; 35: 937-42.
89. Tregellas JR, Tanabe J, Rojas DC, et al. Effects of an α7-nicotinic agonist on default network activity in schizophrenia. Biol Psychiatry 2011; 69: 7-11.
90. NCT01400477. Nicotinic receptors and schizophrenia. Available at http://clinicaltrials.gov/ct2/show/NCT01400477. [Accessed August 1, 2013].
91. Wallace TL, Callahan PM, Tehim A, et al. RG3487, a novel nicotinic α7 receptor partial agonist, improves cognition and sensorimotor gating in rodents. J Pharmacol Exp Ther 2011; 336: 242-53.
92. Rezvani AH, Kholdebarin E, Brucato FH, Callahan PM, Lowe DA, Levin ED. Effect of R3487/MEM3454, a novel nicotinic α7 receptor partial agonist and 5-HT3 antagonist on sustained attention in rats. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 269-75.
93. Hauser TA, Kucinski A, Jordan KG, et al. TC-5619: An α7 neuronal nicotinic receptor-selective agonist that demonstrates efficacy in animal models of the positive and negative symptoms and cognitive dysfunction of schizophrenia. Biochem Pharmacol 2009; 78: 803-12.
94. Lieberman JA, Dunbar G, Segreti AC, et al. A randomized exploratory trial of an α7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia. Neuropsychopharmacology 2013; 38: 968-75.
95. NCT01488929. Efficacy, safety, and tolerability of TC-5619 as augmentation therapy to improve negative symptoms and cognition in outpatients with schizophrenia. Available at http://clinicaltrials.gov/ct2/show/NCT01488929. [Accessed August 1, 2013].
96. Macor JE, Gurley D, Lanthorn T, et al. The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective α7 nicotinic receptor partial agonist. Bioorg Med Chem Lett 2001; 11: 319-21.
97. Papke RL, Porter Papke JK, Rose GM. Activity of α7-selective agonists at nicotinic and serotonin 5HT3 receptors expressed in Xenopus oocytes. Bioorg Med Chem Lett 2004; 14: 1849-53.
98. Hashimoto K, Iyo M, Freedman R, Stevens KE. Tropisetron improves deficient inhibitory auditory processing in DBA/2 mice: role of α7 nicotinic acetylcholine receptors. Psychopharmacology (Berl) 2005; 183: 13-19.
99. Hashimoto K, Fujita Y, Ishima T, Hagiwara H, Iyo M. Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of tropisetron: role of α7 nicotinic receptors. Eur J Pharmacol 2006; 553: 191-5.
100. Kohnomi S, Suemaru K, Goda M, et al. Ameliorating effects of tropisetron on dopaminergic disruption of prepulse inhibition via the α7 nicotinic acetylcholine receptor in Wistar rats. Brain Res 2010; 1353: 152-8.
101. Koike K, Hashimoto K, Takai N, et al. Topisetron improves deficits in auditory P50 suppression in schizophrenia. Schizophr Res 2005; 76: 67-72.
102. Shiina A, Shirayama Y, Niitsu T, et al. A randomised, double-blind, placebo-controlled trial of tropisetron in patients with schizophrenia. Ann Gen Psychiatry 2010; 9: 27.
103. Zhang KY, Liu L, Liu S, et al. Short-term tropisetron treatment and cognitive and P50 auditory gating deficits in schizophrenia. Am J Psychiatry 2012; 169: 974-81.
104. Noroozian M, Ghasemi S, Hosseini SM, et al. A placebo-controlled study of tropisetron added to risperidone for the treatment of negative symptoms in chronic and stable schizophrenia. Psychopharmacology (Berl) 2013; 228: 595-602.
105. NCT00435370. Effectiveness of tropisetron plus risperidone for improving cognitive and perceptual disturbances in schizophrenia. Available at http://clinicaltrials.gov/ct2/show/NCT00435370. [Accessed August 1, 2013].
106. Prickaerts J, van Goethem NP, Chesworth R, et al. EVP-6124, a novel and selective α7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors. Neuropharmacology 2012; 62: 1099-110.
107. Preskorn SH, Gawryl M, Dgetluck N, et al. Normalizing effects of EVP-6124, an α-7 nicotinic partial agonist, on event-related potentials and cognition: a proof of concept, randomized trial in patients with schizophrenia. J Psychiatr Pract 2014; 20: 12-24.
108. Barbier AJ, Hilhorst M, Van Vliet A, et al. Pharmacodynamics, pharmacokinetics, safety, and tolerability of encenicline, a selective α7 nicotinic receptor partial agonist, in single ascending-dose and bioavailability studies. Clin Ther 2015; 37: 311-24.
109. EnVivo Pharmaceutical Ltd. [homepage on the Internet]. EnVivo Pharmaceuticals announces initiation of Phase 3 clinical trial program of EVP-6124 in schizophrenia [February 28, 2013]. Available from: http://www.envivopharma.com/news-item.php?id=45
110. NCT01716975. Study of EVP-6124 (α7 nAChR) as an adjunctive pro-cognitive treatment in schizophrenia subjects receiving chronic stable atypical antipsychotic therapy. Available at http://clinicaltrials.gov/ct2/show/ NCT01716975. [Accessed August 1, 2013].
111. Deardorff WJ, Shobassy A, Grossberg GT. Safety and clinical effects of EVP-6124 in subjects with Alzheimer's disease currently or previously receiving an acetylcholinesterase inhibitor medication. Expert Rev Neurother 2015; 15: 7-17.
112. Chen S, Napier JJ, Zhang GGZ, Brackenmeyer PJ, inventor; Abbott Laboratories, assignee. Novel monohydrate of azaadamantane derivatives. United States patent US 2012/0245195 A1. September 27, 2012.
113. Ritchie C, Robieson W, Pritchett Y, Othman A, Lenz R, Gault L. Efficacy and safety of the α7 agonist ABT-126 in mild-to-moderate Alzheimer's dementia. Alzheimer's Association International Conference, July 13-18, 2013, Boston, MA, USA.
114. NCT01043458. Pharmacokinetic study of ABT-126 in stable subjects with schizophrenia. Available at http://clinicaltrials.gov/ct2/show/ NCT01043458. [Accessed August 1, 2013].
115. NCT01095562. Safety and efficacy study for cognitive deficits in adult subjects with schizophrenia. Available at http://clinicaltrials.gov/ct2/show/ NCT01095562. [Accessed August 1, 2013].
116. NCT01678755. A phase 2 study to evaluate ABT-126 for the treatment of cognitive deficits in schizophrenia. Available at http://clinicaltrials.gov/ct2/show/ NCT01678755. [Accessed August 1, 2013].
117. Feuerbach D, Pezous N, Weiss M, et al. AQW051, a novel, potent and selective α7 nicotinic Ach receptor partial agonist: pharmacological characterization and phase I evaluation. Br J Pharmacol 2015; 172: 1292-304.
118. NCT01163227. Effect of AQW051 on cognitive function in patients with schizophrenia. Available at http://clinicaltrials.gov/ct2/show/ NCT01163227. [Accessed August 1, 2013].
119. NCT01730768. A study to evaluate AQW051 the effects of once daily doses of AQW051 on cognition, in stable schizophrenia patients. Available at http://clinicaltrials.gov/ct2/show/ NCT001730768. [Accessed August 1, 2013].
120. Harris JG, Kongs S, Allensworth D, et al. Effects of nicotine on cognitive deficits in schizophrenia. Neuropsychopharmacology 2004; 29: 1378-85.
121. Bertrand D, Gopalakrishnan M. Allosteric modulation of nicotinic acetylcholine receptors. Biochem Pharmacol 2007; 74: 1155-63.
122. Faghih R, Gopalakrishnan M, Briggs CA. Allosteric modulators of the α7 nicotinic acetylcholine receptor. J Med Chem 2008; 51: 701-12.
123. Williams DK, Wang J, Papke RL. Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: Advantages and limitations. Biochem Pharmacol 2011; 82: 915-30.
124. Timmermann DB, Grønlien JH, Kohlhaas KL, et al. An allosteric modulator of the α7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J Pharmacol Exp Ther 2007; 323: 294-307.
125. Collins T, Young GT, Millar NS. Competitive binding at a nicotinic receptor transmembrane site of two α7-selective positive allosteric modulators with differing effects on agonist-evoked desensitization. Neuropharmacology 2011; 61: 1306-13.
126. Hurst RS, Hajós M, Raggenbass M, et al. A novel positive allosteric modulator of the α7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization. J Neurosci 2005; 25: 4396-4405.
127. Barron SC, McLaughlin JT, See JA, Richards VL, Rosenberg RL. An allosteric modulator of α7 nicotinic receptors, N-(5-Chloro-2, 4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)-urea (PNU-120596), causes conformational changes in the extracellular ligand binding domain similar to those caused by acetylcholine. Mol Pharmacol 2009; 76: 253-63.
128. Munro G, Hansen R, Erichsen H, et al. The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat. Br J Pharmacol 2012; 167: 421-35.
129. Callahan PM, Hutchings EJ, Kille NJ, et al. Positive allosteric modulator of α7 nicotinic-acetylcholine receptors, PNU-120596 augments the effects of donepezil on learning and memory in aged rodents and non-human primates. Neuropharmacology 2013; 67: 201-12.
130. Faghih R, Gopalakrishnan SM, Gronlien JH, et al. Discovery of 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744) as a novel positive allosteric modulator of the alpha7 nicotinic acetylcholine receptor. J Med Chem 2009; 52: 3377-84.
131. Malysz J, Grønlien JH, Anderson DJ, et al. In vitro pharmacological characterization of a novel allosteric modulator of α7 neuronal acetylcholine receptor, 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl) benzenesulfonamide (A-867744), exhibiting unique pharmacological profile. J Pharmacol Exp Ther 2009; 330: 257-67.
132. Dinklo T, Shaban H, Thuring JW, et al. Characterization of 2-[[4-fluoro-3-(trifluoromethyl)phenyl]amino]-4-(4-pyridinyl)-5-thiazolemethanol (JNJ-1930942), a novel positive allosteric modulator of the α7 nicotinic acetylcholine receptor. J Pharmacol Exp Ther 2011; 336: 560-74.
133. Ng HJ, Whittemore ER, Tran MB, et al. Nootropic α7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators. Proc Natl Acad Sci USA 2007; 104: 8059-64.
134. NCT01851603. Phase I Study to Evaluate the Safety and Pharmacokinetics of Oral Doses of Anvylic-3288 in Healthy Subjects (AVL-3288). Available at http://clinicaltrials.gov/ct2/show/NCT01851603. [Accessed August 1, 2013].
135. Winterer G, Gallinant J, Brinkmyer J, et al. Allosteric α7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: A proof-of-mechanism study. Neuropharmacol 2013; 64: 197-204.
136. Wadman M. NIH gambles on recycled drugs. Nature 2013; 499: 263-4.
137. Yang Y, Paspalas CD, Jin LE, Picciotto MR, Arnsten AFT, Wang M. Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolaternal prefrontal cortex. Proc Natl Acad Sci USA 2013; 110: 12078-83.
138. Javitt DC, Zukin SR, Heresco-Levy U, Umbricht D. Has an angel shown the way? Etiological and therapeutic implications of the PCP/NMDA models of schizophrenia. Schizophr Bull 2012; 38: 958-66.
139. Moghaddam B, Javitt D. From revolution to evolution: The gluatamate hypothesis of schizophrenia and its implication for treatment. Neuropsychopharmacology 2012; 37: 4-15.
140. Hashimoto K, Malchow B, Falkai P, Schmitt A. Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders. Eur Arch Psychiatry Clin Nerosci 2013; 263: 367-77.
141. Hashimoto K. Targeting of NMDA receptors in new treatments for schizophrenia. Expert Opin Ther Targets 2014; 18: 1049-63.
142. Hashimoto K. Serine enantiomers as diagnostic biomarkers for schizophrenia and bipolar disorder. Eur Arch Psychiatry Clin Neurosci 2015; DOI 10.1007/s00406-015-0602-4.
143. Wang H, Yu M, Ochani M, et al. Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation. Nature 2003; 421: 384-8.
144. Shytle RD, Mori T, Townsend K, et al. Cholinergic modulation of microglial activation by α7 nicotinic receptors. J Neurochem 2004; 89: 337-43.
145. Gallowitsch-Puerta M, Tracey KJ. Immunologic role of the cholinergic anti-inflammatory pathway and the nicotinic acetylcholine α7 receptor. Ann N Y Acad Sci 2005; 1062: 209-19.
146. Hashimoto K. Microglial activation in schizophrenia and minocycline treatment. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 1758-9.
147. Monji A, Kato T, Kanba S. Cytokines and schizophrenia: Microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci 2009; 63: 257-65.
148. Hashimoto K. Can minocycline prevent the onset of Alzheimer's disease? Ann Neurol 2011; 69: 739-40.
149. Meyer U. Anti-inflammatory signaling in schizophrenia. Brain Behav Immun 2011; 25: 1507-18.
150. Hashimoto K. Emerging role of glutamate in the pathophysiology of major depressive disorder. Brain Res Rev 2009; 61: 105-23.
151. Bredesen DE, John V. Next generation therapeutics for Alzheimer's disease. EMBO Mol Med 2013; 5: 795-8.
152. Hashimoto K. Tropisetron and its targets in Alzheimer's disease. Expert Opin Ther Targets 2015; 19: 1-5.
153. Yang C, Ren Q, Zhang JC, Hashimoto K. Tropisetron for postoperative cognitive decline. Aust NZ J Psychiatry 2015; 49: 662-3.