Selective activation of muscarinic acetylcholine receptors for the treatment of schizophrenia

Current Pharmaceutical Biotechnology

Volumn 13, Issue 8, 2012, Pages 1563-1571

  Dean, B ^a  

^a UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Allosteric agonist; Cortex; Hippocampus; Muscarinic M1 receptor; Muscarinic M4 receptor; Schizophrenia

Indexed keywords

CLOZAPINE; MUSCARINIC M1 RECEPTOR; MUSCARINIC M2 RECEPTOR; MUSCARINIC RECEPTOR; OLANZAPINE; PIRENZEPINE; RADIOLIGAND; TRITIUM;

ALLOSTERISM; ARTICLE; BINDING AFFINITY; BRAIN LEVEL; CENTRAL NERVOUS SYSTEM; CHOLINERGIC TRANSMISSION; COGNITIVE DEFECT; DISEASE ASSOCIATION; DRUG BINDING SITE; FRONTAL CORTEX; HUMAN; LIGAND BINDING; NEGATIVE SYNDROME; NONHUMAN; PATHOPHYSIOLOGY; PHARMACOLOGICAL STIMULATION; POSITIVE SYNDROME; PROTEIN FUNCTION; PROTEIN TARGETING; PSYCHOPHARMACOTHERAPY; PSYCHOSIS; PYRAMIDAL NERVE CELL; RADIOASSAY; RECEPTOR BINDING; SCHIZOPHRENIA;

ANIMALS; ANTIPSYCHOTIC AGENTS; COGNITION DISORDERS; HUMANS; MUSCARINIC AGONISTS; PSYCHOTIC DISORDERS; RECEPTORS, MUSCARINIC; SCHIZOPHRENIA;

EID: 84862594348     PISSN: 13892010     EISSN: 18734316     Source Type: Journal    
DOI: 10.2174/138920112800784970     Document Type: Article

References (119)

1. Brady, L.S.; Winsky, L.; Goodman, W.; Oliveri, M.E; Stover, E. NIMH initiatives to facilitate collaborations among industry, academia, and government for the discovery and clinical testing of novel models and drugs for psychiatric disorders. Neuropsychopharmacology, 2009, 34(1), 229-243.
2. Insel, T.R. Disruptive insights in psychiatry: transforming a clinical discipline. J. Clin. Invest., 2009, 119(4), 700-705.
3. Tamminga, C.A. Accelerating new knowledge in schizophrenia. Am. J. Psychiatry, 2008, 165(8), 949-951.
4. Gale, E.A.The discovery of type 1 diabetes. Diabetes, 2001, 50(2), 217-226.
5. Hewitt, S.M.; Dear, J.; Star, R.A. Discovery of protein biomarkers for renal diseases. J. Am. Soc. Nephrol., 2004, 15(7), 1677-1689.
6. Benson, D.W. Advanvces in cardiovascular genetics and embryology: role of transcription factors in congenital heart disease. Curr. Opin. Pediatr., 2000, 12(5), 497-500.
7. Dean, B. Evolution of the human CNS cholineric system: has this resulted in the emergence of psychiatric disease? Aust. N. Z. J. Psychiatry, 2009, 43(11), 1016-1028.
8. Flynn, D.D.; Ferrari-Dileo, G.; Mash, D.C.; Levey, A.I. Differential regulation of molecular subtypes of molecular subtypes of muscarinic receptors in Alzheimer's disease. J. Neurochem., 1995, 64(4), 1888-1891.
9. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders IV. Washington, DC, 1994.
10. Owen, F.; Cross, A.J.; Crow, T.J.; Lofthouse, R.; Poulter, M. Neurotransmitter receptors in brain in schizophrenia. Acta. Psychiatr. Scand. Suppl., 1981, 291, 20-28.
11. Watanabe, S.; Nishikawa, T.; Takashima, M.; Toru, M. Increased muscarinic cholinergic receptors in prefrontal cortices of medicated schizophrenics. Life Sci., 1983, 33(22), 2187-2196.
12. Hulme, E.C.; Birdsall, N.J.; Buckley, N.J. Muscarinic receptor subtypes. Annu. Rev. Pharmacol. Toxicol., 1990, 30, 633-673.
13. Dean, B.; Crook, J.M.; Opeskin, K.; Hill, C.; Keks, N.; Copolov, D.L. The density of muscarinic M1 receptors is decreased in the caudate-putamen of subjects with schizophrenia. Mol. Psychiatry, 1996, 1(1), 54-58.
14. Crook, J.M.; Tomaskovic-Crook, E.; Copolov, D.L.; Dean, B. Low muscarinic receptor binding in prefrontal cortex from subjects with schizophrenia: a study of Brodmann's areas 8, 9, 10, an 46 and the effects of neuroleptic drug treatment. Am. J. Psychiatry, 2001, 158(6), 918-925.
15. Dean, B.; McLeod, M.; Keriakous, D.; McKenzie, J.; Scarr, E. Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia. Mol. Psychiatry, 2002, 7(10), 1083-1091.
16. Zavitsanou, K.; Katsifis, A.; Filomena, M.; Xu-Feng, H. Investigation of m1/m4 muscarinic receptors in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression disorder. Neuropsychopharmacology, 2004, 29, 619-625.
17. Scarr, E.; Cowie, T.F.; Kanellakis, S.; Sundram, S.; Pantelis, C.; Dean, B. Decreased cortical muscarinic receptors define a subgroup of subjects with schizophrenia. Mol. Psychiatry, 2009, 14(11), 1017-1023.
18. Newell, K.A.; Zavitsanou, K.; Jew, S.K.; Huang, X.F. Alterations of muscarinic and GABA receptor binding in the posterior cingulate cortex in schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2007, 31(1), 225-233.
19. Crook, J.M.; Tomaskovic-Crook, E.; Copolov, D.L.; Dean, B. Decreased muscarinic receptor binding in subjects with schizophrenia: a study of the human hippocampal formation. Biol. Psychiatry, 2000, 48(5), 381-388.
20. Scarr, E.; Sundram, S.; Keriakous, D.; Dean, B. Altered hippocampal muscarinic M4, but not M1, receptor expression from subjects with schizophrenia. Biol. Psychiatry, 2007, 61(10), 1161-1170.
21. Dean, B.; Gray, L.; Keriakous, D.; Scarr, E. A comparison of M1 and M4 muscarinic receptors in the thalamus from control subjects and subjects with schizophrenia. Thalamus and Related Systems, 2004, 2(4), 287-295.
22. Terry, A.V., Jr.; Gearhart, D.A.; Mahadik, S.P.; Warsi, S.; Waller, J.L. Chronic treatment with first or second generation antipsychotics in rodents: effects on high affinity nicotinic and muscarinic acetylcholine receptors in the brain. Neuroscience, 2006, 140(4), 1277-1287.
23. Zavitsanou, K.; Nguyen, V.H.; Han, M.; Huang, X.F. Effects of typical and atypical antipsychotic drugs on rat brain muscarinic receptors. Neurochem. Res., 2007, 32(3), 525-532.
24. Han, M.; Newell, K.; Zavitsanou, K.; Deng, C.; Huang, X.F. Effects of antipsychotic medication on muscarinic M1 receptor mRNA expression in the rat brain. J. Neurosci. Res., 2008, 86(2), 457-464.
25. Gibbons, A.S.; Scarr, E.; McLean, C.; Sundram, S.; Dean, B. Decreased muscarinic receptor binding in the frontal cortex of bipolar disorder and major depressive disorder subjects. J. Affect. Disord., 2009, 116(3), 184-191.
26. Raedler, T.J.; Knable, M.B.; Jones, D.W.; Urbina, R.A.; Gorey, J.G.; Lee, K.S.; Egan, M.F.; Coppola, R.; Weinberger, D.R. In vivo determination of muscarinic acetylcholine receptor availability in schizophrenia. Am. J. Psychiatry, 2003, 160(1), 118-127.
27. Dean, B.; Pavey, G.; Opeskin, K. [3H]raclopride binding to brain tissue from subjects with schizophrenia: methodological aspects. Neuropharmacology, 1997, 36(6), 779-786.
28. Scarr, E.; Dean, B. Muscarinic receptors: do they have a role in the pathology and treatment of schizophrenia? J. Neurochem., 2008, 107(5), 1188-1195.
29. Mancama, D.; Arranz, M.J.; Landau, S.; Kerwin, R. Reduced expression of the muscarinic 1 receptor cortical subtype in schizophrenia. Am. J. Med. Genet. B. Neuropsychiatr. Genet., 2003, 119(1), 2-6.
30. Scarr, E.; Keriakous, D.; Crossland, N.; Dean, B. No change in cortical muscarinic M2, M3 receptors or [35S]GTPgammaS binding in schizophrenia. Life Sci., 2006, 78(11), 1231-1237.
31. Dean, B.; Crook, J.M.; Pavey, G.; Opeskin, K.; Copolov, D.L. Muscarinic1 and 2 receptor mRNA in the human caudate-putamen: no change in m1 mRNA in schizophrenia. Mol. Psychiatry, 2000, 5(2), 203-207.
32. Dorje, F.; Wess, J.; Lambrecht, G.; Tacke, R.; Mutschler, E.; Brann, M.R. Antagonist binding profiles of five clones human muscarinic receptor subtypes. J. Pharmacol. Exp. Ther., 1991, 256(2), 727-733.
33. Miller, J.H.; Gibson, V.A.; McKinney, M. Binding of [3H]AF-DX 384 to cloned and native muscarinic receptors. J. Pharmacol. Exp. Ther., 1991, 259(2), 601-607.
34. Crook, J.M.; Dean, B.; Pavey, G.; Copolov, D. The binding of [3H]AF-DX 384 is reduced in the caudate-putamen of subjects with schizophrenia. Life Sci., 1999, 64(19), 1761-1771.
35. Zavitsanou, K.; Katsifis, A.; Yu, Y.; Huang, X.F. M2/M4 muscarinic receptor binding in the anterior cingulate cortex in schizophrenia and mood disorders. Brain Res. Bull., 2005, 65(5), 397-403.
36. Salah-Uddin, H.; Scarr, E.; Pavey, G.; Harris, K.; Hagan, J.J.; Dean, B.; Challiss, R.A.; Watson, J.M. Altered M(1) muscarinic acetylcholine receptor (CHRM1)-Galpha(q/11) coupling in a schizophrenia endophenotype. Neuropsychopharmacology, 2009, 34(9), 2156-2166.
37. Spalding, T.A.; Trotter, C.; Skjaerbaek, N.; Messier, T.L.; Currier, E.A.; Burstein, E.S.; Li, D.; Hacksell, U.; Brann, M.R. Discovery of an ectopic activation site on the M(1) muscarinic receptor. Mol. Pharmacol., 2002, 61(6), 1297-1302.
38. Langmead, C.J.; Christopoulos, A. Allosteric agonists of 7TM receptors: expanding the pharmacological toolbox. Trends Pharmacol. Sci., 2006, 27(9), 475-481.
39. Felder, C.C. Muscarinic acetylcholine receptors: signal transduction through multiple effectors. FASEB J., 1995, 9(8), 619-625.
40. Felder, C.C.; Porter, A.C.; Skillman, T.L.; Zhang, L.; Bymaster, F.P.; Nathanson, N.M.; Hamilton, S.E.; Gomeza, J.; Wess, J; McKinzie, D.L. Elucidating the role of muscarinic receptors in psychosis. Life Sci., 2001, 68(22-23), 2605-2613.
41. Dean, B. M1 receptor agonism, a possible treatment for cognitive deficits in schizophrenia. Neuropsychopharmacology, 2004, 29(8), 1583-1584.
42. Cohen, L.H.; Thale, T.; Tissenbaum, M.J. Acetylcholine Treatment of Schizophrenia. Arch. Neurol. Psychiatr., 1944, 51(2), 171-175.
43. Siman, R.G.; Klein, W.L. Cholinergic activity regulates muscarinic receptors in central nervous system cultures. Proc. Natl. Acad. Sci. USA, 1979, 76(8), 4141-4145.
44. Neu, C.; DiMascio, A.; Demirgian, E. Antiparkinsonian medication in the treatment of extrapyramidal side-effects: single or multiple daily doses? Curr. Ther. Res. Clin. Exp., 1972, 14(5), 246-251.
45. Nopoulos, P.; Flashman, L.; Flaum, M.; Arndt, S.; Andreasen, N. Stability of cognitive functioning early in the course of schizophrenia. Schizophr. Res., 1994, 14(1), 29-37.
46. Tracy, J.I.; Monaco, C.; Giovannetti, T.; Abraham, G.; Josiassen, R.C. Anticholinergicity and cognitive processing in chronic schizophrenia. Biol. Psychol., 2001, 56(1), 1-22.
47. Vinogradov, S.; Fisher, M.; Warm, H.; Holland, C.; Kirshner, M.A.; Pollock, B.G. The cognitive cost of anticholinergic burden: decreased response to cognitive training in schizophrenia. Am. J. Psychiatry, 2009, 166(9), 1055-1062.
48. Minzenberg, M.J.; Poole, J.H.; Benton, C.; Vinogradov, S. Association of anticholinergic load with impairment of complex attention and memory in schizophrenia. Am. J. Psychiatry, 2004, 161(1), 116-124.
49. Drimer, T.; Shahal, B.; Barak, Y. Effects of discontinuation of long-term anticholinergic treatment in elderly schizophrenia patients. Int. Clin. Psychopharmacol., 2004, 19(1), 27-29.
50. Peuskens, J.; Demily, C.; Thibaut, F. Treatments of cognitive dysfunction in schizophrenia. Clin. Ther., 2005, 27(Suppl A), S25-S37.
51. Leucht, S.; Corves, C.; Arbter, D.; Engel, R.R.; Li, C.; Davis, J.M. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet, 2009, 373(9657), 31-41.
52. Bymaster, F.P.; Hemrick-Luecke, S.K.; Perry, K.W.; Fuller, R.W. Neurochemical evidence for antagonism by olanzapine of dopamine, serotonin, alpha 1-adrenergic and muscarinic receptors in vivo in rats. Psychopharmacology (Berl.), 1996, 124(1-2), 87-94.
53. Meltzer, H.Y.; McGurk, S.R. The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr. Bull., 1999, 25(2), 233-255.
54. Weiner, D.M.; Meltzer, H.Y.; Veinbergs, I.; Donohue, E.M.; Spalding, T.A.; Smith, T.T.; Mohell, N.; Harvey, S.C.; Lameh, J.; Nash, N.; Vanover, K.E.; Olsson, R.; Jayathilake, K.; Lee, M.; Levey, A.I.; Hacksell, U.; Burstein, E.S.; Davis, R.E.; Brann, M.R. The role of M1 muscarinic receptor agonism of Ndesmethylclozapine in the unique clinical effects of clozapine. Psychopharmacology (Berl.), 2004, 177(1-2), 207-216.
55. Pereira, A.; McLaren, A.; Bell, W.R.; Copolov, D.; Dean B. Potential clozapine target sites on peripheral hematopoietic cells and stromal cells of the bone marrow. Pharmacogenomics J., 2003, 3(4), 227-234.
56. Pereira, A.; Dean, B. Clozapine bioactivation induces dosedependent, drug-specific toxicity of human bone marrow stromal cells: a potential in vitro system for the study of agranulocytosis. Biochem. Pharmacol., 2006, 72(6), 783-793.
57. Combs, M.D.; Perry, P.J.; Bever, K.A. N-desmethylclozapine, an insensitive marker of clozapine-induced agranulocytosis and granulocytopenia. Pharmacotherapy, 1997, 17(6), 1300-1304.
58. Meltzer, H.Y. New drugs for the treatment of schizophrenia. Psychiatr. Clin. N. Am., 1993, 16(2), 365-385.
59. Copolov, D.L.; Bell, W.R.; Benson, W.J.; Keks, N.A.; Strazzeri, D.C.; Johnson, G.F. Clozapine treatment in Australia: a review of haematological monitoring. Med. J. Aust., 1998, 168(10), 495-497.
60. Anon. ACADIA Pharmaceuticals Announces Results from ACP- 104 Phase IIb Schizophrenia Trial. http://www.drugs.com/clinical_trials/acadia-pharmaceuticals-announces-results-acp-104-phase-iib-schizophrenia-trial-4810.html#ixzz0naCBgfBh. [Accessed 2008].
61. Thomas, D.R.; Dada, A.; Jones, G.A.; Deisz, R.A.; Gigout, S.; Langmead, C.J.; Werry, T.D.; Hendry, N.; Hagan, J.J.; Davies, C.H.; Watson, J.M. N-desmethylclozapine (NDMC) is an antagonist at the human native muscarinic M(1) receptor. Neuropharmacology, 2010, 58(8), 1206-1214.
62. Gray, L.; McOmish, C.; Scarr, E.; Dean, B.; Hannan, A.J. Role of muscarinic receptors in the activity of N-desmethylclozapine: reversal of hyperactivity in the phospholipase C knockout mouse. Behav. Pharmacol., 2008, 19(5-6), 543-547.
63. Natesan, S.; Reckless, G.E.; Barlow, K.B.; Nobrega, J.N.; Kapur, S. Evaluation of N-desmethylclozapine as a potential antipsychotic--preclinical studies. Neuropsychopharmacology, 2007, 32(7), 1540-1549.
64. Gray, J.A.; Roth, B.L. The pipeline and future of drug development in schizophrenia. Mol. Psychiatry, 2007, 12(10), 904-922.
65. Zeng, X.P.; Le, F.; Richelson, E. Muscarinic m4 receptor activation by some atypical antipsychotic drugs. Eur. J. Pharmacol., 1997, 321(3), 349-354.
66. Leach, K.; Loiacono, R.E.; Felder, C.C.; McKinzie, D.L.; Mogg, A.; Shaw, D.B.; Sexton, P.M.; Christopoulos, A. Molecular mechanisms of action and in vivo validation of an M4 muscarinic acetylcholine receptor allosteric modulator with potential antipsychotic properties. Neuropsychopharmacology, 2010, 35(4), 855-869.
67. Sullivan, R.J.; Andres, S.; Otto, C.; Miles, W.; Kydd, R. The effects of an indigenous muscarinic drug, Betel nut (Areca catechu), on the symptoms of schizophrenia: a longitudinal study in Palau, Micronesia. Am. J. Psychiatry, 2007 164(4), 670-673.
68. Sullivan, R.J.; Allen, J.S.; Otto, C.; Tiobech, J.; Nero K. Effects on chewing betel nut (Areca catechu) on the symptoms of people with schizophrenia in Palau, Micronesia. Br. J. Psychiatry, 2000, 177, 174-178.
69. Bales, A.; Peterson, M.J.; Ojha, S.; Upadhaya, K.; Adhikari, B.; Barrett, B. Associations between betel nut (Areca catechu) and symptoms of schizophrenia among patients in Nepal: A longitudinal study. Psychiatry Res., 2009, 169(3), 203-211.
70. Thomas, R.L.; Langmead, C.J.; Wood, M.D.; Challiss, R.A. Contrasting effects of allosteric and orthosteric agonists on m1 muscarinic acetylcholine receptor internalization and downregulation. J. Pharmacol. Exp. Ther., 2009, 331(3), 1086-1095.
71. Shekhar, A.; Potter, W.Z.; Lightfoot, J.; Lienemann, J.; Dube, S.; Mallinckrodt, C.; Bymaster, F.P.; McKinzie, D.L.; Felder, C.C. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am. J. Psychiatry, 2008, 165(8), 1033-1039.
72. Shannon, H.E.; Rasmussen, K.; Bymaster, F.P.; Hart, J.C.; Peters, S.C.; Swedberg, M.D.; Jeppesen, L.; Sheardown, M.J.; Sauerberg, P.; Fink-Jensen, A. Xanomeline, an M(1)/M(4) preferring muscarinic cholinergic receptor agonist, produces antipsychoticlike activity in rats and mice. Schizophr. Res., 2000, 42(3), 249-259.
73. Stanhope, K.J.; Mirza, N.R.; Bickerdike, M.J.; Bright, J.L.; Harrington, N.R.; Hesselink, M.B.; Kennett, G.A.; Lightowler, S.; Sheardown, M.J.; Syed, R.; Upton, R.L.; Wadsworth, G.; Weiss, S.M.; Wyatt, A. The muscarinic receptor agonist xanomeline has an antipsychotic-like profile in the rat. J. Pharmacol. Exp. Ther., 2001, 299(2), 782-792.
74. Andersen, M.B.; Fink-Jensen, A.; Peacock, L.; Gerlach, J.; Bymaster, F.; Lundbaek, J.A.; Werge, T. The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys. Neuropsychopharmacology, 2003, 28(6), 1168-1175.
75. Jakubik, J.; Michal, P.; Machova, E.; Dolezal, V. Importance and prospects for design of selective muscarinic agonists. Physiol. Res., 2008, 57(Suppl 3), S39-S47.
76. Veroff, A.E.; Bodick, N.C.; Offen, W.W.; Sramek, J.J.; Cutler, N.R. Efficacy of xanomeline in Alzheimer disease: cognitive improvement measured using the Computerized Neuropsychological Test Battery (CNTB). Alzheimer Dis. Assoc. Disord., 1998, 12(4), 304-312.
77. Liao, D.L.; Hong, C.J.; Chen, H.M.; Chen, Y.E.; Lee, S.M.; Chang, C.Y.; Chen, H.; Tsai, S.J. Association of muscarinic m1 receptor genetic polymorphisms with psychiatric symptoms and cognitive function in schizophrenic patients. Neuropsychobiology, 2003, 48(2), 72-76.
78. Dean, B.; Bymaster, F.P.; Scarr, E. Muscarinic receptors in schizophrenia. Curr. Mol. Med., 2003, 3(5), 419-426.
79. Wess, J. Muscarinic acetylcholine receptor knockout mice: novel phenotypes and clinical implications. Annu. Rev. Pharmacol. Toxicol., 2004, 44, 423-450.
80. Anagnostaras, S.G.; Murphy, G.G.; Hamilton, S.E.; Mitchell, S.L.; Rahnama, N.P.; Nathanson, N.M.; Silva, A.J. Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice. Nat. Neurosci., 2003, 6(1), 51-58.
81. Shirey, J.K.; Brady, A.E.; Jones, P.J.; Davis, A.A.; Bridges, T.M.; Kennedy, J.P.; Jadhav, S.B.; Menon, U.N.; Xiang, Z.; Watson, M.L.; Christian, E.P.; Doherty, J.J.; Quirk, M.C.; Snyder, D.H.; Lah, J.J.; Levey, A.I.; Nicolle, M.M.; Lindsley, C.W.; Conn, P.J. A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in recersal learning. J. Neurosci., 2009, 29(45), 14271-14286.
82. Gulledge, A.T.; Bucci, D.J.; Zhang, S.S.; Matsui, M.; Yeh, H.H. M1 receptors mediate cholinergic modulation of excitability in neocortical pyramidal neurons. J. Neurosci., 2009, 29(31), 9888-9902.
83. Andreasen, N.C.; O'Leary, D.S.; Flaum, M.; Nopoulos, P.; Watkins, G.L.; Boles, Ponto, L.L.; Hichwa, R.D. Hypofrontality in schizophrenia: distributed dysfunctional circuits in neurolepticnaÏve patients. Lancet, 1997, 349(9067), 1730-1734.
84. Pantelis, C.; Barnes, T.R. Drug strategies and treatment-resistant schizophrenia. Aust. N. Z. J. Psychiatry, 1996, 30(1), 20-37.
85. Howes, O.D.; Egerton, A.; Allan, V.; McGuire, P.; Stokes, P.; Kapur, S. Mechanisms underlying psychosis and antipsychotic treatment response in schizophrenia: insights from PET ans SPECT imaging. Curr. Pharm. Des., 2009, 15(22), 2550-2559.
86. Zorn, S.H.; Jones, S.B.; Ward, K.M.; Liston, D.R. Clozapine is a potent and selective muscarinic M4 receptor agonist. Eur. J. Pharmacol., 1994, 269(3), R1-R2.
87. Bymaster, F.P.; Shannon, H.E.; Rasmussen, K.; DeLapp, N.W.; Mitch, C.H.; Ward, J.S.; Calligaro, D.O.; Ludvigsen, T.S.; Sheardown, M.J.; Olesen, P.H.; Swedberg, M.D.; Sauerberg, P.; Fink-Jensen, A. Unexpected antipsychotic-like activity with the muscarinic receptor ligand (5R,6R)6-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]octane. Eur. J. Pharmacol., 1998, 356(2-3), 109-119.
88. Brady, A.E.; Jones, C.K.; Bridges, T.M.; Kennedy, J.P.; Thompson, A.D.; Heiman, J.U.; Breininger, M.L.; Gentry, P.R.; Yin, H.; Jadhav, S.B.; Shirey, J.K.; Conn, P.J.; Lindsley, C.W. Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats. J. Pharmacol. Exp. Ther., 2008, 327(3), 941-953.
89. Jeon, J.; Dencker, D.; Wortwein, G.; Woldbye, D.P.; Cui, Y.; Davis, A.A.; Levey, A.I.; Schutz, G.; Sager, T.N.; Mork, A.; Li, C.; Deng, C.X.; Fink-Jensen, A.; Wess, J. A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors. J. Neurosci., 2010, 30(6), 2396-2405.
90. Tzavara, E.T.; Bymaster, F.P.; Davis, R.J.; Wade, M.R.; Perry, K.W.; Wess, J.; McKinzie, D.L.; Felder, C.; Nomikos, G.G. M4 muscarinic receptors regulate the dynamics of cholinergic and dopaminergic neurotransmission: relevance to the pathophysiology and treatment of related CNS pathologies. FASEB J., 2004, 18(12), 1410-1412.
91. Bymaster, F.P.; Felder, C.C. Role of the cholinergic muscarinic system in bipolar disorder and related mechanism of action of antipsychotic agents. Mol. Psychiatry, 2002, 7(Suppl. 1), S57-S63.
92. Volpicelli-Daley, L.A.; Duysen, E.G.; Lockridge, O.; Levey, A.I. Altered hippocampal muscarinic receptors in acetylcholinesterasedeficient mice. Ann. Neurol., 2003, 53(6), 788-796.
93. Hootman, S.R.; Kuroiwa, C.L.; Habara, Y. Muscarinic receptor desensitization and downregulation induced by full and partial cholinergic agonists in rat pancreatic acini. Pancreas, 1989, 4(3), 315-322.
94. Lenz, W.; Petrusch, C.; Jakobs, K.H.; van Koppen, C.J. Agonistinduced down-regulation of the m4 muscarinic acetylcholine receptor occurs without changes in receptor mRNA steady-state levels. Naunyn Schmiedebergs Arch. Pharmacol., 1994, 350(5), 507-513.
95. Wei, H.B.; Yamamura, H.I.; Roeske, W.R. Down-regulation and desensitization of the muscarinic M1 and M2 receptors in transfected fibroblast B82 cells. Eur. J. Pharmacol., 1994, 268(3), 381-391.
96. Mullaney, I.; Dodd, M.W.; Buckley, N.; Milligan, G. Agonist activation of transfected human M1 muscarinic acetylcholine receptors in CHO cells results in down-regulation of both the receptor and the alpha subunit of the G-protein Gq. Biochem. J., 1993, 289(pt. 1), 125-131.
97. Wang, S.Z.; Hu, J.R.; Long, R.M.; Pou, W.S.; Forray, C.; el-Fakahany, E.E. Agonist-induced down-regulation of m1 muscarinic receptors and reduction of their mRNA level in a transfected cell line. FEBS Lett., 1990, 276(1-2), 185-188.
98. el-Fakahany, E.E.; Lee, J.H. Agonist-induced muscarinic acetylcholine receptor down-regulation in intact rat brain cells. Eur. J. Pharmacol., 1986, 132(1), 21-30.
99. Conn, P.J.; Christopoulos, A.; Lindsley, C.W. Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nat. Rev. Drug Discov., 2009, 8(1), 41-54.
100. Espinoza-Fonseca, L.M.; Trujillo-Ferrara, J.G. Identification of multiple allosteric sites on the M1 muscarinic acetylcholine receptor. FEBS Lett., 2005, 579(30), 6726-6732.
101. Holzgrabe, U.; Bender, W.; Cid, H.M.; Staudt, M.; Pick, R.; Pfletschinger, C.; Balatkova, E.; Trankle, C.; Mohr, K. Ligands for the common allosteric site of acetylcholine M2-receptors: development and application. Pharm. Acta. Helv., 2000, 74(2-3), 149-155.
102. Jooste, E.H.; Sharma, A.; Zhang, Y.; Emala, C.W. Rapacuronium augments acetylcholine-induced bronchoconstriction via positive allosteric interactions at the M3 muscarinic receptor. Anesthesiology, 2005, 103(6), 1195-1203.
103. Kennedy, J.P.; Bridges, T.M.; Gentry, P.R.; Brogan, J.T.; Kane, A.S.; Jones, C.K.; Brady, A.E.; Shirey, J.K.; Conn, P.J.; Lindsley, C.W. Synthesis and structure-activity relationships of allosteric potentiators of the m(4) muscarinic acetylcholine receptor. Chem. Med. Chem., 2009, 4(10), 1600-1607.
104. Bridges, T.M.; Kennedy, J.P.; Cho, H.P.; Breininger, M.L.; Gentry, P.R.; Hopkins, C.R.; Conn, P.J.; Lindsley, C.W. Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM. Bioorg. Med. Chem. Lett., 2010, 20(2), 558-562.
105. Marlo, J.E.; Niswender, C.M.; Days, E.L.; Bridges, T.M.; Xiang, Y.; Rodriguez, A.L.; Shirey, J.K.; Brady, A.E.; Nalywajko, T.; Luo, Q.; Austin, C.A.; Williams, M.B.; Kim, K.; Williams, R.; Orton, D.; Brown, H.A.; Lindsley, C.W.; Weaver, C.D.; Conn, P.J. Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity. Mol. Pharmacol., 2009, 75(3), 577-588.
106. Chan, W.Y.; McKinzie, D.L.; Bose, S.; Mitchell, S.N.; Witkin, J.M.; Thompson, R.C.; Christopoulos, A.; Lazareno, S.; Birdsall, N.J.; Bymaster, F.P.; Felder, C.C. Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia. Proc. Natl. Acad. Sci. USA, 2008, 105(31), 10978-0983.
107. Lebon, G.; Langmead, C.J.; Tehan, B.G.; Hulme, E.C. Mutagenic mapping suggests a novel binding mode for selective agonists of M1 muscarinic acetylcholine receptors. Mol. Pharmacol., 2009, 75(2), 331-341.
108. Spalding, T.A.; Ma, J.N.; Ott, T.R.; Friberg, M.; Bajpai, A.; Bradley, S.R.; Davis, R.E.; Brann, M.R.; Burstein, E.S. Structural requirements of transmembrane domain 3 for activation by the M1 muscarinic receptor agonists AC-42, AC260584, clozapine, and Ndesmethylclozapine: evidence for three distinct modes of receptor activation. Mol. Pharmacol., 2006, 70(6), 1974-1983.
109. Langmead, C.J.; Austin, N.E.; Branch, C.L.; Brown, J.T.; Buchanan, K.A.; Davies, C.H.; Forbes, I.T.; Fry, V.A.; Hagan, J.J.; Herdon, H.J.; Jones, G.A.; Jeggo, R.; Kew, J.N.; Mazzali, A.; Melarange, R.; Patel, N.; Pardoe, J.; Randall, A.D.; Roberts, C.; Roopun, A.; Starr, K.R.; Teriakidis, A.; Wood, M.D.; Whittington, M.; Wu, Z. and Watson, J. Characterization of a CNS penetrant, selective M1 muscarinic receptor agonist, 77-LH-28-1. Br. J. Pharmacol., 2008, 154(5), 1104-1115.
110. Jones, C.K.; Brady, A.E.; Davis, A.A.; Xiang, Z.; Bubser, M.; Tantawy, M.N.; Kane, A.S.; Bridges, T.M.; Kennedy, J.P.; Bradley, S.R.; Peterson, T.E.; Ansari, M.S.; Baldwin, R.M.; Kessler, R.M.; Deutch, A.Y.; Lah, J.J.; Levey, A.I.; Lindsley, C.W.; Conn, P.J. Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in rats. J. Neurosci., 2008, 28(41), 10422-10433.
111. Thomas, R.L.; Mistry, R.; Langmead, C.J.; Wood, M.D.; Challiss, R.A. G protein coupling and signaling pathway activation by m1 muscarinic acetylcholine receptor orthosteric and allosteric agonists. J. Pharmacol. Exp. Ther., 2008, 327(2), 365-374.
112. Bradley, S.R.; Lameh, J.; Ohrmund, L.; Son, T.; Bajpai, A.; Nguyen, D.; Friberg, M.; Burstein, E.S.; Spalding, T.A.; Ott, T.R.; Schiffer, H.H.; Tabatabaei, A.; McFarland, K.; Davis, R.E.; Bonhaus, D.W. AC-260584, an orally bioavailable M(1) muscarinic receptor allosteric agonist, improves cognitive performance in an animal model. Neuropharmacology, 2010, 58(2), 365-373.
113. Weinberger, D.R.; Berman, K.F.; Suddath, R.; Torrey, E.F. Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins. Am. J. Psychiatry, 1992, 149(7), 890-897.
114. Nawaratne, V.; Leach, K.; Suratman, N.; Loiacono, R.E.; Felder, C.C.; Armbruster, B.N.; Roth, B.L.; Sexton, P.M.; Christopoulos, A. New insights into the function of M4 muscarinic acetylcholine receptors gained using a novel allosteric modulator and a DREADD (designer receptor exclusively activated by a designer drug). Mol. Pharmacol., 2008, 74(4), 1119-1131.
115. Shirey, J.K.; Xiang, Z.; Orton, D.; Brady, A.E.; Johnson, K.A.; Williams, R.; Ayala, J.E.; Rodriguez, A.L.; Wess, J.; Weaver, D.; Niswender, C.M.; Conn, P.J. An allosteric potentiator of M4 mAChR modulates hippocampal synaptic transmission. Nat. Chem. Biol., 2008, 4(1), 42-50.
116. Li, B.; Woo, R.S.; Mei, L.; Malinow, R. The neuregulin-1 receptor erbB4 controls glutamatergic synapse maturation and plasticity. Neuron, 2007, 54(4), 583-597.
117. Steullet, P.; Neijt, H.C.; Cuenod, M.; Do, K.Q. Synaptic plasticity impairment and hypofunction of NMDA receptors induced by glutathione deficit: relevance to schizophrenia. Neuroscience, 2006, 137(3), 807-819.
118. Hao, W.; Xing-Jun, W.; Yong-Yao, C.; Liang, Z.; Yang, L.; Hong-Zhuan, C. Up-regulation of M1 muscarinic receptors expressed in CHOm1 cells by panaxynol via cAMP pathway. Neurosci. Lett., 2005, 383(1-2), 121-126.
119. McOmish, C.E.; Burrows, E.; Howard, M.; Scarr, E.; Kim, D.; Shin, H.S.; Dean, B.; van den Buuse, M.; Hannan, A.J. Phospholipase C-beta1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration. Mol. Psychiatry, 2008, 13(7), 661-672.