152
Views
33
CrossRef citations to date
0
Altmetric
Review

Role of the cholinergic system in the pathology and treatment of schizophrenia

&
Pages 73-86 | Published online: 09 Jan 2014

References

  • American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association, Arlington, VA, USA (2000).
  • Lusis AJ, Mar R, Pajukanta P. Genetics of atherosclerosis. Annu. Rev. Genomics Hum. Genet.5, 189–218 (2004)
  • Roth BL, Meltzer HY. The role of serotonin in schizophrenia. In: Psychopharmacology The Fourth Generation of Progress. Bloom FJ, Kupfer DJ (Eds). Raven Press, NY, USA 1215–1229 (1995)
  • Jablensky A. Subtyping schizophrenia: implications for genetic research. Mol. Psychiatry11(9), 815–836 (2006).
  • Hallmayer JF, Kalaydjieva L, Badcock J et al. Genetic evidence for a distinct subtype of schizophrenia characterized by pervasive cognitive deficit. Am. J. Hum. Genet.77(3), 468–476 (2005).
  • Pantelis C, Barnes TR. Drug strategies and treatment-resistant schizophrenia. Aust. NZ J. Psychiatry30(1), 20–37 (1996).
  • Roth BL, Sheffler DJ, Kroeze WK. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nat. Rev. Drug Discov.3(4), 353–359 (2004).
  • Kapur S, Mizrahi R, Li M. From dopamine to salience to psychosis – linking biology, pharmacology and phenomenology of psychosis. Schizophr. Res.79(1), 59–68 (2005).
  • Wooley DW, Shaw E. A biological and pharmacological suggestion about certain mental disorders. Proc. Natl Acad. Sci. USA40, 228–231 (1954).
  • KimJS, Kornhuber HH, Schmid-Burgk W, Holzmuller B. Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci. Lett.20(3), 379–382 (1980).
  • Luisada PV. The phencyclidine psychosis: phenomenology and treatment. NIDA Res. Monogr.21, 241–253 (1978).
  • Laruelle M, Frankle WG, Narendran R, Kegeles LS, Abi-Dargham A. Mechanism of action of antipsychotic drugs: from dopamine D2 receptor antagonism to glutamate NMDA facilitation. Clin. Ther.27(Suppl. 1), S16–S24 (2005).
  • Laruelle M, Kegeles LS, Abi-Dargham A. Glutamate, dopamine, and schizophrenia: from pathophysiology to treatment. Ann NY Acad. Sci.1003, 138–158 (2003).
  • Carlsson A. The current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacology1(3), 179–186 (1988).
  • Geyer MA, Vollenweider FX. Serotonin research: contributions to understanding psychoses. Trends Pharmacolol. Sci. DOI: 10.1176/appi.ajp.2008.06091591 (2008) (Epub ahead of print).
  • Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am. J. Psychiatry153(3), 321–330 (1996).
  • Green MF, Kern RS, Heaton RK. Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS. Schizophr. Res.72(1), 41–51 (2004).
  • Gold JM. Cognitive deficits as treatment targets in schizophrenia. Schizophr. Res.72(1), 21–28 (2004).
  • Heinrichs RW, Zakzanis KK. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology12(3), 426–445 (1998).
  • Peuskens J, Demily C, Thibaut F. Treatment of cognitive dysfunction in schizophrenia. Clin. Ther.27(Suppl. 1), S25–S37 (2005).
  • Gray JA, Roth BL. The pipeline and future of drug development in schizophrenia. Mol. Psychiatry12(10), 904–922 (2007).
  • Lucas-Meunier E, Fossier P, Baux G, Amar M. Cholinergic modulation of the cortical neuronal network. Pflugers Archiv. Eur. J. Physiol.446(1), 17–29 (2003).
  • Wessler I, Kirkpatrick C, Racké K. The cholinergic “pitfall”: acetylcholine, a universal cell molecule in biological systems, including humans. Clin. Exp. Pharmacol. Physiol.26(3), 198–205 (1999).
  • Shepherd GM. Neurobiology. Oxford University Press, Inc., Oxford, UK (1998).
  • Okuda T, Haga T, Kanai Y, Endou H, Ishihara T, Katsura I. Identification and characterization of the high-affinity choline transporter. Nat. Neurosci.3(2), 120–125 (2000).
  • Masson J, Sagne C, Hamon M, Mestikawy SE. Neurotransmitter transporters in the central nervous system. Pharmacol. Rev.51(3), 439–464 (1999).
  • Hoffman BB, Taylor P. Neurotransmission: the autonomic and somatic motor nervous systems. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics. Hardman JG, Limbard LE, Gilman AG (Eds). McGraw-Hill, NY, USA 115–155 (2001).
  • Perry E, Walker M, Grace J, Perry R. Acetylcholine in mind: a neurotransmitter correlate of consciousness? Trends Neurosci.22(6), 273–280 (1999).
  • Dale HH. The action of certain esters and ethers of choline and their relation to muscarine. J. Pharmacol. Exp. Ther.6(2), 147–190 (1914).
  • Steinlein OK, Bertrand D. Neuronal nicotinic acetylcholine receptors: from the genetic analysis to neurological diseases. Biochem. Pharmacol.76(10), 1175–1183 (2008).
  • Albuquerque EX, Pereira EF, Mike A, Eisenberg HM, Maelicke A, Alkondon M. Neuronal nicotinic receptors in synaptic functions in humans and rats: physiological and clinical relevance. Behav. Brain Res.113(1–2), 131–141 (2000).
  • Zolles G, Wagner E, Lampert A, Sutor B. Functional expression of nicotinic acetylcholine receptors in rat neocortical layer 5 pyramidal cells. Cereb. Cortex DOI: 10.1093/cercor/bhn158 (2008) (Epub ahead of print).
  • Gotti C, Zoli M, Clementi F. Brain nicotinic acetylcholine receptors: native subtypes and their relevance. Trends Pharmacol. Sci.27(9), 482–491 (2006).
  • Bonner TI, Buckley NJ, Young AC, Brann MR. Identification of a family of muscarinic acetylcholine receptor genes. Science237(4814), 527–532 (1987).
  • Langmead CJ, Watson J, Reavill C. Muscarinic acetylcholine receptors as CNS drug targets. Pharmacol. Ther.117(2), 232–243 (2008).
  • Mrzljak L, Levey AI, Goldman-Rakic PS. Association of m1 and m2 muscarinic receptor proteins with asymmetric synapses in the primate cerebral cortex: morphological evidence for cholinergic modulation of excitatory neurotransmission. Proc. Natl Acad. Sci. USA90(11), 5194–5198 (1993).
  • Zhang W, Basile AS, Gomeza J, Volpicelli LA, Levey AI, Wess J. Characterization of central inhibitory muscarinic autoreceptors by the use of muscarinic acetylcholine receptor knock-out mice. J. Neurosci.22(5), 1709–1717 (2002).
  • Flynn DD, Ferrari-DiLeo G, Mash DC, Levey AI. Differential regulation of molecular subtypes of muscarinic receptors in Alzheimer’s disease. J. Neurochem.64(4), 1888–1891 (1995).
  • Weiner DM, Levey AI, Brann MR. Expression of muscarinic acetylcholine and dopamine receptor mRNAs in rat basal ganglia. Proc. Natl Acad. Sci. USA87(18), 7050–7054 (1990).
  • Wess J, Duttaroy A, Zhang W et al. M1–M5 muscarinic receptor knockout mice as novel tools to study the physiological roles of the muscarinic cholinergic system. Recept. Channels9(4), 279–290 (2003).
  • Dean B, Bymaster FP, Scarr E. Muscarinic receptors in schizophrenia. Curr. Mol. Med.3(5), 419–426 (2003).
  • Li Z, Huang M, Ichikawa J, Dai J, Meltzer HY. N-desmethylclozapine, a major metabolite of clozapine, increases cortical acetylcholine and dopamine release in vivo via stimulation of m (1) muscarinic receptors. Neuropsychopharmacology30(11), 1986–1995 (2005).
  • Li Z, Snigdha S, Roseman AS, Dai J, Meltzer HY. Effect of muscarinic receptor agonists xanomeline and sabcomeline on acetylcholine and dopamine efflux in the rat brain; comparison with effects of 4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one (AC260584) and N-desmethylclozapine. Eur. J. Pharmacol.596(1-3), 89–97 (2008).
  • Volz TJ, Farnsworth SJ, Rowley SD, Hanson GR, Fleckenstein AE. Methylphenidate-induced increases in vesicular dopamine sequestration and dopamine release in the striatum: the role of muscarinic and dopamine D2 receptors. J. Pharmacol. Exp. Ther.327(1), 161–167 (2008).
  • Grilli M, Patti L, Robino F, Zappettini S, Raiteri M, Marchi M. Release-enhancing pre-synaptic muscarinic and nicotinic receptors co-exist and interact on dopaminergic nerve endings of rat nucleus accumbens. J. Neurochem. DOI: 10.1111/j.1471–4159.2008.05307.x (2008) (Epub ahead of print).
  • Lester DB, Miller AD, Pate TD, Blaha CD. Midbrain acetylcholine and glutamate receptors modulate accumbal dopamine release. Neuroreport19(9), 991–995 (2008).
  • Marino MJ, Rouse ST, Levey AI, Potter LT, Conn PJ. Activation of the genetically defined m1 muscarinic receptor potentiates N-methyl-d-aspartate (NMDA) receptor currents in hippocampal pyramidal cells. Proc. Natl Acad. Sci. USA95(19), 11465–11470 (1998).
  • Shinoe T, Matsui M, Taketo MM, Manabe T. Modulation of synaptic plasticity by physiological activation of M1 muscarinic acetylcholine receptors in the mouse hippocampus. J. Neurosci.25(48), 11194–11200 (2005).
  • Kremin T, Gerber D, Giocomo LM, Huang SY, Tonegawa S, Hasselmo ME. Muscarinic suppression in stratum radiatum of CA1 shows dependence on presynaptic M1 receptors and is not dependent on effects at GABA(B) receptors. Neurobiol. Learn. Mem.85(2), 153–163 (2006).
  • Seol GH, Ziburkus J, Huang S et al. Neuromodulators control the polarity of spike-timing-dependent synaptic plasticity. Neuron55(6), 919–929 (2007).
  • Cohen LH, Thale T, Tissenbaum MJ. Acetylcholine treatment of schizophrenia. Arch. Neurol. Psychiatry51, 171–175 (1944).
  • Forrer GR. Atropine toxicity in the treatment of mental disease. Am. J. Psychiatry108(2), 107–112 (1951).
  • Kapur S, Mamo D. Half a century of antipsychotics and still a central role for dopamine D2 receptors. Prog. Neuropsychopharmacol. Biol. Psychiatry27(7), 1081–1090 (2003).
  • Raedler TJ, Bymaster FP, Tandon R, Copolov D, Dean B. Towards a muscarinic hypothesis of schizophrenia. Mol. Psychiatry12(3), 232–246 (2006).
  • Minzenberg MJ, Poole JH, Benton C, Vinogradov S. Association of anticholinergic load with impairment of complex attention and memory in schizophrenia. Am. J. Psychiatry161(1), 116–124 (2004).
  • Friedhoff AJ, Alpert M. A dopaminergic–cholinergic mechanism in production of psychotic symptoms. Biol. Psychiatry6(2), 165–169 (1973).
  • Janowsky DS, Davis JM, El Yousef MK, Sekerke HJ. Antagonistic effects of physostigmine and methylphenidate in man. Am. J. Psychiatry130(12), 1370–1376 (1973).
  • Tandon R, Greden JF. Cholinergic hyperactivity and negative schizophrenic symptoms. A model of cholinergic/dopaminergic interactions in schizophrenia. Arch. Gen. Psychiatry46(8), 745–753 (1989).
  • Yeomans JS. Role of tegmental cholinergic neurons in dopaminergic activation, antimuscarinic psychosis and schizophrenia. Neuropsychopharmacology12(1), 3–16 (1995).
  • Hughes JR, Frances RJ. How to help psychiatric patients stop smoking. Psychiatry Serv.46(5), 435–436 (1995).
  • Adler LE, Hoffer LJ, Griffith J, Waldo MC, Freedman R. Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics. Biol. Psychiatry32(7), 607–616 (1992).
  • Sacco KA, Bannon KL, George TP. Nicotinic receptor mechanisms and cognition in normal states and neuropsychiatric disorders. J. Psychopharmacol.18(4), 457–474 (2004).
  • 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. USA94(2), 587–592 (1997).
  • Perl O, Ilani T, Strous RD, Lapidus R, Fuchs S. The α7 nicotinic acetylcholine receptor in schizophrenia: decreased mRNA levels in peripheral blood lymphocytes. FASEB J.17(13), 1948–1950 (2003).
  • Perl O, Strous RD, Dranikov A, Chen R, Fuchs S. Low levels of α7-nicotinic acetylcholine receptor mRNA on peripheral blood lymphocytes in schizophrenia and its association with illness severity. Neuropsychobiology53(2), 88–93 (2006).
  • Martin-Ruiz CM, Haroutunian VH, Long P et al. Dementia rating and nicotinic receptor expression in the prefrontal cortex in schizophrenia. Biol. Psychiatry54(11), 1222–1233 (2003).
  • De Luca V, Likhodi O, Van Tol HH, Kennedy JL, Wong AH. Regulation of α7-nicotinic receptor subunit and α7-like gene expression in the prefrontal cortex of patients with bipolar disorder and schizophrenia. Acta Psychiatr. Scand.114(3), 211–215 (2006).
  • Lipska BK, Mitkus S, Caruso M et al. RGS4 mRNA expression in postmortem human cortex is associated with COMT Val158Met genotype and COMT enzyme activity. Hum. Mol. Genet.15(18), 2804–2812 (2006).
  • Mathew SV, Law AJ, Lipska BK et al. α7 nicotinic acetylcholine receptor mRNA expression and binding in postmortem human brain are associated with genetic variation in neuregulin 1. Hum. Mol. Genet.16(23), 2921–2932 (2007).
  • Severance EG, Yolken RH. Novel α7 nicotinic receptor isoforms and deficient cholinergic transcription in schizophrenia. Genes Brain Behav.7(1), 37–45 (2008).
  • Freedman R, Leonard S, Waldo M, Gault J, Olincy A, Adler LE. Characterization of allelic variants at chromosome 15q14 in schizophrenia. Genes Brain Behav.5, 14–22 (2006).
  • Gault J, Hopkins J, Berger R et al. Comparison of polymorphisms in the a7 nicotinic receptor gene and its partial duplication in schizophrenic and control subjects. Am. J. Med. Genet. B Neuropsychiatr. Genet.123B(1), 39–49 (2003).
  • Li CH, Liao HM, Chen CH. Identification of molecular variants at the promoter region of the human α7 neuronal nicotinic acetylcholine receptor subunit gene but lack of association with schizophrenia. Neurosci. Lett.372(1–2), 1–5 (2004).
  • Zammit S, Spurlock G, Williams H et al. Genotype effects of CHRNA7, CNR1 and COMT in schizophrenia: interactions with tobacco and cannabis use. Br. J. Psychiatry191, 402–407 (2007).
  • Iwata Y, Nakajima M, Yamada K et al. Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia. Neurosci. Res.57(2), 194–202 (2007).
  • De Luca V, Wang H, Squassina A, Wong GW, Yeomans J, Kennedy JL. Linkage of M5 muscarinic and α7-nicotinic receptor genes on 15q13 to schizophrenia. Neuropsychobiology50(2), 124–127 (2004).
  • De Luca V, Wong AH, Muller DJ, Wong GW, Tyndale RF, Kennedy JL. Evidence of association between smoking and α7 nicotinic receptor subunit gene in schizophrenia patients. Neuropsychopharmacology29(8), 1522–1526 (2004).
  • Houy E, Raux G, Thibaut F et al. The promoter -194 C polymorphism of the nicotinic α 7 receptor gene has a protective effect against the P50 sensory gating deficit. Mol. Psychiatry9(3), 320–322 (2004).
  • Martin LF, Leonard S, Hall MH, Tregellas JR, Freedman R, Olincy A. Sensory gating and α-7 nicotinic receptor gene allelic variants in schizoaffective disorder, bipolar type. Am. J. Med. Genet. B Neuropsychiatr. Genet.144B(5), 611–614 (2007).
  • Levin ED, Simon BB. Nicotinic acetylcholine involvement in cognitive function in animals. Psychopharmacology (Berl.)138(3–4), 217–230 (1998).
  • Wonnacott S, Sidhpura N, Balfour DJ. Nicotine: from molecular mechanisms to behaviour. Curr. Opin. Pharmacol.5(1), 53–59 (2005).
  • Breese CR, Lee MJ, Adams CE et al. Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia. Neuropsychopharmacology23(4), 351–364 (2000).
  • De Luca V, Voineskos S, Wong G, Kennedy JL. Genetic interaction between α4 and β2 subunits of high affinity nicotinic receptor: analysis in schizophrenia. Exp. Brain Res.174(2), 292–296 (2006).
  • Kishi T, Ikeda M, Kitajima T et al. Genetic association analysis of tagging SNPs in α4 and β2 subunits of neuronal nicotinic acetylcholine receptor genes (CHRNA4 and CHRNB2 ) with schizophrenia in the Japanese population. J. Neural Transm.115, 1457–1461 (2008).
  • Faraone SV, Su J, Taylor L, Wilcox M, Van Eerdewegh P, Tsuang MT. A novel permutation testing method implicates sixteen nicotinic acetylcholine receptor genes as risk factors for smoking in schizophrenia families. Hum. Hered.57(2), 59–68 (2004).
  • Voineskos S, De Luca V, Mensah A, Vincent JB, Potapova N, Kennedy JL. Association of α4β2 nicotinic receptor and heavy smoking in schizophrenia. J. Psychiatry Neurosci.32(6), 412 (2007).
  • 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. Neuropsychopharmacology28(3), 542–551 (2003).
  • Koike K, Hashimoto K, Takai N et al. Tropisetron improves deficits in auditory P50 suppression in schizophrenia. Schizophr. Res.76(1), 67–72 (2005).
  • Adler LE, Cawthra EM, Donovan KA et al. Improved P50 auditory gating with ondansetron in medicated schizophrenia patients. Am. J. Psychiatry162(2), 386–388 (2005).
  • Olincy A, Harris JG, Johnson LL et al. Proof-of-concept trial of an α7 nicotinic agonist in schizophrenia. Arch. Gen. Psychiatry63(6), 630–638 (2006).
  • Freedman R, Olincy A, Buchanan RW et al. Initial Phase 2 trial of a nicotinic agonist in schizophrenia. Am. J. Psychiatry165(8), 1040–1047 (2008).
  • Barr RS, Culhane MA, Jubelt LE et al. The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls. Neuropsychopharmacology33(3), 480–490 (2008).
  • Bora E, Veznedaroglu B, Kayahan B. The effect of galantamine added to clozapine on cognition of five patients with schizophrenia. Clin. Neuropharmacol.28(3), 139–141 (2005).
  • Schubert MH, Young KA, Hicks PB. Galantamine improves cognition in schizophrenic patients stabilized on risperidone. Biol. Psychiatry60(6), 530–533 (2006).
  • Lee SW, Lee JG, Lee BJ, Kim YH. A 12-week, double-blind, placebo-controlled trial of galantamine adjunctive treatment to conventional antipsychotics for the cognitive impairments in chronic schizophrenia. Int. Clin. Psychopharmacol.22(2), 63–68 (2007).
  • Buchanan RW, Conley RR, Dickinson D et al. Galantamine for the treatment of cognitive impairments in people with schizophrenia. Am. J. Psychiatry165(1), 82–89 (2008).
  • Kelly DL, McMahon RP, Weiner E et al. Lack of beneficial galantamine effect for smoking behavior: a double-blind randomized trial in people with schizophrenia. Schizophr. Res.103(1–3), 161–168 (2008).
  • Dyer MA, Freudenreich O, Culhane MA et al. High-dose galantamine augmentation inferior to placebo on attention, inhibitory control and working memory performance in nonsmokers with schizophrenia. Schizophr. Res.102(1–3), 88–95 (2008).
  • Deutsch SI, Schwartz BL, Schooler NR, Rosse RB, Mastropaolo J, Gaskins B. First administration of cytidine diphosphocholine and galantamine in schizophrenia: a sustained α7 nicotinic agonist strategy. Clin. Neuropharmacol.31(1), 34–39 (2008).
  • Bennett JP Jr, Enna SJ, Bylund DB, Gillin JC, Wyatt RJ, Snyder SH. Neurotransmitter receptors in frontal cortex of schizophrenics. Arch. Gen. Psychiatry36(9), 927–934 (1979).
  • Bolden C, Cusack B, Richelson E. Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J. Pharmacol. Exp. Ther.260(2), 576–580 (1992).
  • Moriya H, Takagi Y, Nakanishi T, Hayashi M, Tani T, Hirotsu I. Affinity profiles of various muscarinic antagonists for cloned human muscarinic acetylcholine receptor (mAChR) subtypes and mAChRs in rat heart and submandibular gland. Life Sci.64(25), 2351–2358 (1999).
  • ZavitsanouK, Katsifis A, Mattner F, Xu-Feng H. Investigation of m1/m4 muscarinic receptors in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression disorder. Neuropsychopharmacology29(3), 619–625 (2004).
  • Deng C, Huang XF. Decreased density of muscarinic receptors in the superior temporal gyrus in schizophrenia. J. Neurosci. Res.81(6), 883–890 (2005).
  • Matsumoto I, Inoue Y, Iwazaki T, Pavey G, Dean B. 5-HT2A and muscarinic receptors in schizophrenia: a postmortem study. Neurosci. Lett.379(3), 164–168 (2005).
  • Dean B, McLeod M, Keriakous D, McKenzie J, Scarr E. Decreased muscarinic (1) receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia. Mol. Psychiatry7(10), 1083–1091 (2002).
  • Mancama D, Arranz MJ, Landau S, Kerwin R. Reduced expression of the muscarinic 1 receptor cortical subtype in schizophrenia. Am. J. Med. Genet. B Neuropsychiatr. Genet.119(1), 2–6 (2003).
  • Zavitsanou K, Katsifis A, Yu Y, Huang XF. M2/M4 muscarinic receptor binding in the anterior cingulate cortex in schizophrenia and mood disorders. Brain Res. Bull.65(5), 397–403 (2005).
  • Newell KA, Zavitsanou K, Jew SK, Huang XF. Alterations of muscarinic and GABA receptor binding in the posterior cingulate cortex in schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry31(1), 225–233 (2007).
  • Scarr E, Keriakous D, Crossland N, Dean B. No change in cortical muscarinic M2, M3 receptors or [35S]GTPγS binding in schizophrenia. Life Sci.78(11), 1231–1237 (2006).
  • Tzavara ET, Bymaster FP, Felder CC et al. Dysregulated hippocampal acetylcholine neurotransmission and impaired cognition in M2, M4 and M2/M4 muscarinic receptor knockout mice. Mol. Psychiatry8(7), 673–679 (2003).
  • Scarr E, Sundram S, Keriakous D, Dean B. Altered hippocampal muscarinic M4, but not M1, receptor expression from subjects with schizophrenia. Biol. Psychiatry61, 1161–1170 (2007).
  • Raedler TJ, Knable MB, Jones DW et al.In vivo determination of muscarinic acetylcholine receptor availability in schizophrenia. Am. J. Psychiatry160(1), 118–127 (2003).
  • Scarr E, Cowie TF, Kanellakis S, Sundram S, Pantelis C, Dean B. Decreased cortical muscarinic receoptors define a subgroup of subjects with schizophrenia. Mol. Psychiatry DOI: 10.1038/mp.2008.28 (2008) (Epub ahead of print).
  • McKinney M, Anderson D, Vella-Rountree L. Different agonist-receptor active conformations for rat brain M1 and M2 muscarinic receptors that are separately coupled to two biochemical effector systems. Mol. Pharmacol.35(1), 39–47 (1989).
  • Salles J, Wallace MA, Fain JN. Differential effects of alkylating agents on the multiple muscarinic receptor subtypes linked to activation of phospholipase C by carbachol in rat brain cortical membranes. J. Pharmacol. Exp. Ther.264(2), 521–529 (1993).
  • Fisher SK, Snider RM. Differential receptor occupancy requirements for muscarinic cholinergic stimulation of inositol lipid hydrolysis in brain and in neuroblastomas. Mol. Pharmacol.32(1), 81–90 (1987).
  • Weiner DM, Meltzer HY, Veinbergs I et al. The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine. Psychopharmacology (Berl.)177(1–2), 207–216 (2004).
  • Shekhar A, Potter WZ, Lightfoot J et al. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am. J. Psychiatry165(8), 1033–1039
  • Shannon HE, Bymaster FP, Calligaro DO et al. Xanomeline: a novel muscarinic receptor agonist with functional selectivity for M1 receptors. J. Pharmacol. Exp. Ther.269(1), 271–281 (1994).
  • Watson J, Brough S, Coldwell MC et al. Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. Br. J. Pharmacol.125(7), 1413–1420 (1998).
  • Böhm SK, Grady EF, Bunnett NW. Regulatory mechanisms that modulate signalling by G-protein-coupled receptors. Biochem. J.322(1), 1–18 (1997).
  • May LT, Lin Y, Sexton PM, Christopoulos A. Regulation of M2 muscarinic acetylcholine receptor expression and signaling by prolonged exposure to allosteric modulators. J. Pharmacol. Exp. Ther.312(1), 382–390 (2005).
  • Langmead CJ, Austin NE, Branch CL et al. Characterization of a CNS penetrant, selective M1 muscarinic receptor agonist, 77-LH-28-21. Br. J. Pharmacol.154(5), 1104–1115 (2008).
  • Chan WY, McKinzie DL, Bose S et al. Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia. Proc. Natl Acad. Sci. USA105(31), 10978–10983 (2008).
  • Scarr E, Dean B. Muscarinic receptors: do they have a role in the pathology and treatment of schizophrenia? J. Neurochem.107(5), 1188–1195 (2008).
  • Lenzi A, Maltinti E, Poggi E, Fabrizio L, Coli E. Effects of rivastigmine on cognitive function and quality of life in patients with schizophrenia. Clin. Neuropharmacol.26(6), 317–321 (2003).
  • MendelsohnE, Rosenthal M, Bohiri Y, Werber E, Kotler M, Strous RD. Rivastigmine augmentation in the management of chronic schizophrenia with comorbid dementia: an open-label study investigating effects on cognition, behaviour and activities of daily living. Int. Clin. Psychopharmacol.19(6), 319–324 (2004).
  • Aasen I, Kumari V, Sharma T. Effects of rivastigmine on sustained attention in schizophrenia: an FMRI study. J. Clin. Psychopharmacol.25(4), 311–317 (2005).
  • Kumari V, Aasen I, Ffytche D, Williams SCR, Sharma T. Neural correlates of adjunctive rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind fMRI study. Neuroimage29(2), 545–556 (2006).
  • Sharma T, Reed C, Aasen I, Kumari V. Cognitive effects of adjunctive 24-weeks Rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind investigation. Schizophr. Res.85(1–3), 73–83 (2006).
  • Chouinard S, Stip E, Poulin J et al. Rivastigmine treatment as an add-on to antipsychotics in patients with schizophrenia and cognitive deficits. Curr. Med. Res. Opin.23(3), 575–583 (2007).
  • Freudenreich O, Herz L, Deckersbach T et al. Added donepezil for stable schizophrenia: a double-blind, placebo-controlled trial. Psychopharmacology181(2), 358–363 (2005).
  • Kohler CG, Martin EA, Kujawski E, Bilker W, Gur RE, Gur RC. No effect of donepezil on neurocognition and social cognition in young persons with stable schizophrenia. Cognit. Neuropsychiatry12(5), 412–421 (2007).
  • Fagerlund B, Soholm B, Fink-Jensen A, Lublin H, Glenthoj BY. Effects of donepezil adjunctive treatment to ziprasidone on cognitive deficits in schizophrenia: a double-blind, placebo-controlled study. Clin. Neuropharmacol.30(1), 3–12 (2007).
  • Lee BJ, Lee JG, Kim YH. A 12-week, double-blind, placebo-controlled trial of donepezil as an adjunct to haloperidol for treating cognitive impairments in patients with chronic schizophrenia. J. Psychopharmacol.21(4), 421–427 (2007).
  • Keefe RSE, Malhotra AK, Meltzer HY et al. Efficacy and safety of donepezil in patients with schizophrenia or schizoaffective disorder: significant placebo//practice effects in a 12-week, randomized, double-blind, placebo-controlled trial. Neuropsychopharmacology33(6), 1217–1228 (2007).
  • Akhondzadeh S, Gerami M, Noroozian M et al. A 12-week, double-blind, placebo-controlled trial of donepezil adjunctive treatment to risperidone in chronic and stable schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry32(8), 1810–1815 (2008).
  • Sanchez-MorlaEM, Garcia-Jimenez MA, Barabash A et al. P50 sensory gating deficit is a common marker of vulnerability to bipolar disorder and schizophrenia. Acta Psychiatr. Scand.117(4), 313–318 (2008).
  • Erskine FF, Ellis JR, Ellis KA et al. Evidence for synergistic modulation of early information processing by nicotinic and muscarinic receptors in humans. Hum. Psychopharmacol.19(7), 503–509 (2004).
  • Green A, Ellis KA, Ellis J et al. Muscarinic and nicotinic receptor modulation of object and spatial n-back working memory in humans. Pharmacol. Biochem. Behav.81(3), 575–584 (2005).
  • Ellis JR, Ellis KA, Bartholomeusz CF et al. Muscarinic and nicotinic receptors synergistically modulate working memory and attention in humans. Int. J. Neuropsychopharmacol.9(2), 175–189 (2006).
  • Spalding TA, Trotter C, Skjarbak N et al. Discovery of an ectopic activation site on the m1 muscarinic receptor. Mol. Pharmacol.61(6), 1297–1302 (2002).
  • Langmead CJ, Fry VAH, Forbes IT et al. Probing the molecular mechanism of interaction between 4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl]-piperidine (AC-42) and the muscarinic m1 receptor: direct pharmacological evidence that ac-42 is an allosteric agonist. Mol. Pharmacol.69(1), 236–246 (2006).
  • Acker BA, Jacobsen EJ, Rogers BN et al. Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carnonamide as an agonist of the α7 nicotinic acetylcholine receptor: in vitro and in vivo activity. Bioorg. Med. Chem. Lett.18(12), 3611–3615 (2008).
  • Timmermann DB, Gronlien JH, Kohlhaas KL et al. An allosteric modulator of the α7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J. Pharmacol. Exp. Ther.323(1), 294–307 (2007).
  • Watson J, Langmead C, Davies C, Hagan J. Challenges in developing cholinergic agents for the treatment of schizophrenia. Int. J. Neuropsychopharmacol.11(Suppl. 1), 31 (2008)
  • Brady AE, Jones CK, Bridges TM et al. Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats. J. Pharmacol. Exp. Ther.327(3), 941–953 (2008).
  • Thomas RL, Mistry R, Langmead CJ, Wood MD, Challiss RJ. G protein coupling and signaling pathway activation by m1 muscarinic acetylcholine receptor orthosteric and allosteric agonists. J. Pharmacol. Exp. Ther.327(2), 365–374 (2008).

Website

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.