Skip to main content Accessibility help
×
Home
Hostname: page-component-768ffcd9cc-96qlp Total loading time: 1.059 Render date: 2022-11-30T08:13:48.017Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "displayNetworkTab": true, "displayNetworkMapGraph": false, "useSa": true } hasContentIssue true

Muscarinic Agonists for the Treatment of Cognition in Schizophrenia

Published online by Cambridge University Press:  07 November 2014

Abstract

It is widely accepted that cholinergic activity at muscarinic receptors is required to maintain cognitive functions, including learning and memory. Memory domains are especially impaired in schizophrenia, which may explain difficulties in psychosocial rehabilitation of individuals with this illness. However, little is known about the mechanism of this impairment. To understand our current knowledge, we reviewed the literature since 1990 via a PubMed search for the terms “muscarinic”, “schizophrenia” “cognition,” “memory,” “learning,” and “agonist” in combination. We found 89 basic science/laboratory studies, case reports/series, case-control studies, cross-sectional studies, standardized controlled animal trials, standardized controlled human trials, and reviews. Although further research is required to fully understand the neuropharmacology of the cholinergic system in cognitive function in schizophrenia, we have examined the data currently available. In general, these data suggest that agonist activity at acetylcholine muscarinic type 1 (M1) receptors would enhance memory and learning in schizophrenia. We present an overview of likely side effects of muscarinic agonists. We outline the anticholinergic activity of several available antipsychotics and review the available M1 muscarinic agonists.

Type
Review Articles
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Hyman, SE, Fenton, WS. Medicine: what are the right targets for psychopharmacology? Science. 2003;299:350351.CrossRefGoogle ScholarPubMed
2.Green, MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996;153:321330.Google Scholar
3.Mohs, RC. Assessing cognitive function in schizophrenics and patients with Alzheimer's disease. Schizophr Res. 1995;17(1):115121.CrossRefGoogle ScholarPubMed
4.Saykin, AJ, Gur, RC, Gur, RE, et al.Neuropsychological function in schizophrenia. Selective impairment in memory and learning. Arch Gen Psychiatry. 1991;48(7):618624.CrossRefGoogle ScholarPubMed
5.Saykin, AJ, Shtasel, DL, Gur, RE, et al.Neuropsychological deficits in neuroleptic naive patients with first-episode schizophrenia. Arch Gen Psychiatry. 1994;51(2):124131.CrossRefGoogle ScholarPubMed
6.Weickert, TW, Goldberg, TE. First- and second-generation antipsychotic medication and cognitive processing in schizophrenia. Curr Psychiatry Rep. 2005;7(4):304310.CrossRefGoogle Scholar
7.Carter, CS, Braver, TS, Barch, DM, et al.Anterior cingulate cortex, error detection, and the online monitoring of performance. Science. 1998;280(5364):747749.CrossRefGoogle Scholar
8.Carter, CS, Perlstein, W, Ganguli, R, et al.Functional hypofrontality and working memory dysfunction in schizophrenia. Am J Psychiatry. 1998;155(9):12851287.CrossRefGoogle Scholar
9.Friedman, JI, Adler, DN, Howanitz, E, et al.A double blind placebo controlled trial of donepezil adjunctive treatment to risperidone for the cognitive impairment of schizophrenia. Biol Psychiatry. 2002;51:349357.CrossRefGoogle ScholarPubMed
10.Peuskens, J, Demily, C, Thibaut, F. Treatment of cognitive dysfunction in schizophrenia. Clin Ther. 2005;27(suppl 1):S25S37.CrossRefGoogle Scholar
11.Keefe, RS, Bilder, RM, Davis, SM, et al;CATIE Investigators; Neurocognitive Working Group. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry. 2007;64(6):633647.CrossRefGoogle Scholar
12.Keefe, RS, Eesley, CE, Poe, MP. Defining a cognitive function decrement in schizophrenia. Biol Psychiatry. 2005;15;57(6):688691.CrossRefGoogle Scholar
13.Keefe, RS, Bilder, RM, Harvey, PD, et al.Baseline neurocognitive deficits in the CATIE schizophrenia trial. Neuropsychopharmacology. 2006;31(9):20332046.CrossRefGoogle ScholarPubMed
14.Marder, SR. The NIMH-MATRICS project for developing cognition-enhancing agents for schizophrenia. Dialogues Clin Neurosci. 2006;8(1):109113.Google Scholar
15.Kern, RS, Nuechterlein, KH, Green, MF, et al.The MATRICS Consensus Cognitive Battery, part 2: co-norming and standardization. Am J Psychiatry. 2008;165(2):214220.CrossRefGoogle ScholarPubMed
16.Nuechterlein, KH, Barch, DM, Gold, JM, et al.Identification of separable cognitive factors in schizophrenia. Schizophr Res. 2004;72(1):2939.CrossRefGoogle Scholar
17.Nuechterlein, KH, Green, MF, Kern, RS, et al.The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. Am J Psychiatry. 2008;65(2):203213.CrossRefGoogle Scholar
18.Buchanan, RW, Summerfelt, A, Tek, C, Gold, J. An open-labeled trial of adjunctive donepezil for cognitive impairments in patients with schizophrenia. Schizophr Res. 2002;59:2933.CrossRefGoogle Scholar
19.Friedman, JI. Cholinergic targets for cognitive enhancement in schizophrenia: focus on cholinesterase inhibitors and muscarinic agonists. Psychopharmacology (Berl). 2004;174(1):4553.CrossRefGoogle ScholarPubMed
20.Eglen, RM. Muscarinic receptor subtypes in neuronal and non-neuronal cholinergic function. Auton Autacoid Pharmacol. 2006;26(3):219233.CrossRefGoogle ScholarPubMed
21.Dean, B, McLeod, M, Keriakous, D, McKenzie, J, Scarr, E. Decreased muscarinic receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia. Mol Psychiatry. 2002;7:10831091.CrossRefGoogle ScholarPubMed
22.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 M1 muscarinic receptors. Neuropsychopharmacology. 2005;30(11):19861995.CrossRefGoogle Scholar
23.Anagnostaras, SG, Murphy, GG, Hamilton, SE, et al.Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice. Nat Neurosci. 2003;6(1):5158.CrossRefGoogle ScholarPubMed
24.Wess, J. Muscarinic acetylcholine receptor knockout mice: novel phenotypes and clinical implications. Annu Rev Pharmacol Toxicol. 2004;44(1):423450.CrossRefGoogle ScholarPubMed
25.Bymaster, FP, Felder, CC, Tzavara, E, et al.Muscarinic mechanisms of antipsychotic atypicality. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27(7):11251143.CrossRefGoogle ScholarPubMed
26.Wess, J, Eglen, RM, Gautam, D. Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development. Nat Rev Drug Discov. 2007;6:721733.CrossRefGoogle ScholarPubMed
27.Pinkas-Kramarski, R, Stein, R, Undenboim, L, Sokolovsky, M. Growth factor-like effects mediated by muscarinic receptors in PC12M1 cells. J Neurochem. 1992;59(6):21582166.CrossRefGoogle ScholarPubMed
28.Lindenboim, L, Pinkas-Kramarski, R, Sokolovsky, M, Stein, R. Activation of muscarinic receptors inhibits apoptosis in PC12M1 cells. J Neurochem. 1995;64:24912499.CrossRefGoogle ScholarPubMed
29.Van Der Zee, EA, Luiten, PGM. Muscarinic acetycholine receptors in the hippocampus, neocortex and amygdala: A review of immunocytochemical localization in relation to learning and memory. Prog Neurobiol. 1999;58:409471.CrossRefGoogle Scholar
30.Aura, J, Sirvio, J, Riekkinen, P Jr.Methoctramine moderately improves memory but pirenzepine disrupts performance in delayed non-matching to position test. Eur J Pharmacol. 1997;333:129134.CrossRefGoogle ScholarPubMed
31.McDonald, MP, Willard, LB, Wenk, GL, Crawley, JN. Coadministration of galanin antagonist M40 with a muscarinic M1 agonist improves delayed nonmatching to position choice accuracy in rats with cholinergic lesions. J Neurosci. 1998;18:50785085.CrossRefGoogle ScholarPubMed
32.Terry, AV, Buccafusco, JJ, Borsini, F, Leusch, A. Memory-related task performance by aged rhesus monkeys administered the muscarinic M1-preferring agonist, talsaclidine. Psychopharmacology. 2002;162(3):292300.CrossRefGoogle Scholar
33.Fisher, A, Brandeis, R, Chapman, S, Pittel, Z, Michaelson, DM, (). M1 muscarinic agonist treatment reverses cognitive and cholinergic impairments of apolipoprotein E-deficient mice. J Neurochem. 1998;70:19911997.CrossRefGoogle ScholarPubMed
34.Ruske, AC, White, KG. Facilitation of memory performance by a novel muscarinic agonist in young and old rats. Pharmacol Biochem Behav. 1999;63(4):663667.CrossRefGoogle Scholar
35.Brandeis, R, Sapir, M, Hafif, N, et al.AF150(S): A new functionally selective M1 agonist improves cognitive performance in rats. Pharmacol Biochem Behav. 1995;51(4):667674.CrossRefGoogle ScholarPubMed
36.Hyde, TM, Crook, JM. Cholinergic systems and schizophrenia: primary pathology or epiphenomena? J Chem Neuroanat. 2001;22:5363.CrossRefGoogle ScholarPubMed
37.Levey, AI, Edmunds, SM, Koliatsps, V, Wiley, RG, Heilman, CJ. Expression of m1-m4 muscarinic acetycholine receptor proteins in rat hippocampus and regulation by cholinergic innervation. J Neurosci. 1995;15(5):40774092.CrossRefGoogle Scholar
38.Bymaster, FP, Felder, C, Ahmed, S, McKinzie, D. Muscarinic receptors as a target for drugs treating schizophrenia. Curr Drug Targets CNS Neurol Disord. 2002;1(2):163181.CrossRefGoogle ScholarPubMed
39.Crook, JM, Tomaskovic-Crook, E, Copolov, DL, Dean, B. Decreased muscarinic receptor binding in subjects with schizophrenia: a study of the human hippocampal formation. Biol Psychiatry. 2000;48:381388.CrossRefGoogle ScholarPubMed
40.Eglen, RM, Choppin, A, Dillon, MP, Hegde, S. Muscarinic receptor ligands and their therapeutic potential. Curr Opin Chem Biol. 1999;3(4):426432.CrossRefGoogle ScholarPubMed
41.Friedman, JI, Temporini, H, Davis, KL. Pharmacologic strategies for augmenting cognitive performance in schizophrenia. Biol Psychiatry. 1999;45:116.CrossRefGoogle Scholar
42.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. 2003l119B:26.CrossRefGoogle Scholar
43.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):12311237.CrossRefGoogle Scholar
44.Yeomans, JS. Role of tegmental cholinergic neurons in dopaminergic activation, anti-muscarinic psychosis and schizophrenia. Neuropsychopharmacogy. 1995;12(1):316.CrossRefGoogle Scholar
45.Zavitsanou, K, Katsifis, A, Manner, F, Huang, XF. Investigation of m1/m4 muscarinic receptors in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression disorder. Neuropsychopharmacogy. 2004;29(3):619625.Google ScholarPubMed
46.Raedler, TJ, Knable, MB, Jones, DW, et al.In vivo determination of muscarinic acetylcholine receptor availability in schizophrenia. Am J Psychiatry. 2003;160(1):118–27.CrossRefGoogle Scholar
47.Han, M, Newell, K, Zavitsanou, K, Deng, C, Huang, XF. Effects of antipsychotic medication on muscarinic M1 receptor mRNA expression in the rat brain. J Neurosci Res. 2008;86(2):457–64.CrossRefGoogle ScholarPubMed
48.Sarter, M, Bruno, JP. Cognitive functions of cortical acetylcholine: toward a unifying hypothesis. Brain Res Brain Res Rev. 1997;23(1–2):2846.CrossRefGoogle Scholar
49.Liao, DL, Hong, CH, Chen, HM, et al.Association of muscarinic m1 receptor genetic polymorphisms with psychiatric symptoms and cognitive function in schizophrenic patients. Neuropsychobiology. 2003;48(2):7276.CrossRefGoogle ScholarPubMed
50.Zakzanis, KK, Andrikopoulos, J, Young, DA, Campbell, Z, Sethian, T. Neuropsychological differentiation of late-onset schizophrenia and dementia of the Alzheimer's type. Appl Neuropsychol. 2003;10(2):105114.CrossRefGoogle ScholarPubMed
51.Barch, DM, Carter, CS, Braver, TS, et al.Selective deficits in prefrontal cortex function in medicationnaive patients with schizophrenia. Arch Gen Psychiatry. 2001;58:280288.CrossRefGoogle Scholar
52.Harvey, PD, Keefe, RS. Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry. 2001;158(2):176184.CrossRefGoogle ScholarPubMed
53.Brown, JH, Taylor, P. Muscarinic receptor agonists and antagonists. In: Hardman, JG, Limbird, LE, Gilman, AG, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill Professional; 2001;10(7):155174.Google Scholar
54.Minzenberg, MJ, Poole, JH, Benton, C, Vinogradov, S. Association of anticholinergic load with impairment of complex attention and memory in schizophrenia. Am J Psychiatry. 2004;161:116124.CrossRefGoogle Scholar
55.Davies, MA, Compton-Toth, BA, Hufeisen, SJ, Meltzer, HY, Roth, BL. The highly efficacious actions of N-desmethylclozapine at muscarinic receptors are unique and not a common property of either typical or atypical antipsychotic drugs: is M1 agonism a pre-requisite for mimicking clozapine's actions? Psychiopharmacology. 2005;178(4):451460.CrossRefGoogle ScholarPubMed
56.Abi-Dargham, A, Laruelle, M. Mechanisms of action of second generation antipsychotic drugs in schizophrenia: insights from brain imaging studies. Eur Psychiatry. 2005;20(1):1527.CrossRefGoogle ScholarPubMed
57.Kanba, SSuzuki, E, Nomura, S, et al.Affinity of neuroleptics for D1 receptor of human brain striatum. J Psychiatry Neurosci. 1994;19(4):265269.Google ScholarPubMed
58.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. 2004;177(1–2):207216.CrossRefGoogle ScholarPubMed
59.Wagner, AD, Davachi, L. Cognitive neuroscience: forgetting of things past. Curr Biol. 2001;11(23):R964R967.CrossRefGoogle ScholarPubMed
60.Ellis, JR, Ellis, KA, Bartholomeusz, CF, et al.Muscarinic and nicotinic receptors synergistically modulate working memory and attention in humans. Int J Neuropsychopharmacol. 2006;9(2): 175189.CrossRefGoogle ScholarPubMed
61.Drimer, T, Shahal, B, Barak, Y. Effects of discontinuation of long-term anticholinergic treatment in elderly schizophrenia patients. Int Clin Psychopharmacol. 2004;19:2729.CrossRefGoogle ScholarPubMed
62.Goldsmith, SK, Joyce, JN. Alterations in hippocampal mossy fiber pathway in schizo-phrenia and alzheimer's disease. Biol Psychiatry. 1995;37:122126.CrossRefGoogle Scholar
63.White, KE, Cummings, JL. Schizophrenia and Alzheimer's disease: clinical and pathophysiologic analogies. Compr Psychiatry. 1996;37(3):188195.CrossRefGoogle ScholarPubMed
64.Stryjer, R, Bar, F, Straus, RD, Baruch, Y, Rabey, JM. Donepezil management of schizophrenia with associated dementia. J Clin Psychopharmacol. 2002;22(2):226-229.CrossRefGoogle ScholarPubMed
65.MacEwan, GW, Ehmann, TS, Khanbhai, I, Wrixon, C. Donepezil in schizophrenia–is it helpful? An experimental design case study. Acta Psychiatr Scand. 2001;104(6):469472.CrossRefGoogle Scholar
66.Allen, TB, McEvoy, JP. Galantamine for treatment-resistant schizophrenia. Am J Psychiatry. 2002;159:12441245.CrossRefGoogle ScholarPubMed
67.Buchanan, RW, Conley, RR, Dickinson, D, et al.Galantamine for the treatment of cognitive impairments in people with schizophrenia. Am J Psychiatry. 2008;165(1):8289.CrossRefGoogle ScholarPubMed
68.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 Neuropsychiatry. 2007;12(5):412421.CrossRefGoogle ScholarPubMed
69.Stip, E, Sepehery, AA, Chouinard, S. Add-on therapy with acetylcholinesterase inhibitors for memory dysfunction in schizophrenia: a systematic quantitative review, Part 2. Clin Neuropharmacol. 2007;30(4):218229.Google ScholarPubMed
70.Nahas, Z, George, MS, Horner, MD, et al.Augmenting atypical antipsychotics with a cognitive enhancer (donepezil) improves regional brain activity in schizophrenia patients: a pilot double-blind placebo controlled BOLD fMRI study. Neurocase. 2003;9(3):274282.Google ScholarPubMed
71.Schubert, MH, Young, KA, Hicks, PB. Galantamine improves cognition in schizophrenic patients stabilized on risperidone. Biol Psychiatry. 2006;60(6):530533.CrossRefGoogle ScholarPubMed
72.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. 2007;22(2):6368.CrossRefGoogle ScholarPubMed
73.Raedler, TJ, Knable, MB, Jones, DW, Urbina, RA, Egan, MF, Weinberger, DR. Central muscarinic acetylcholine receptor availability in patients treated with clozapine. Neuropsychopharmacogy. 2003;28:15311537.CrossRefGoogle ScholarPubMed
74.Kay, GG, Abou-Donia, MB, Messer, WS, Murphy, DG, Tsao, JW, Ouslander, JG. Antimuscarinic drugs for overactive bladder and their potential effects on cognitive function in older patients. J Am Geriatr Soc. 2005;53(12):21952201.CrossRefGoogle ScholarPubMed
75.Bartolomeo, AC, Morris, H, Buccafusco, JJ, et al.The preclinical pharmacological profile of WAY-132983, a potent M1 preferring agonist. J Pharmacol Exp Ther. 2000;292(2):584596.Google ScholarPubMed
76.Bodick, NC, Offen, WW, Levey, AI, et al.Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch Neurol. 1997;54(4):465473.CrossRefGoogle ScholarPubMed
77.Guitton, C, Abbar, M, Kinowski, J-M, Chabrand, P, Bressolle, F. Multiple-dose pharmacokinetics of clozapine in patients with chronic schizophrenia. J Clinical Psychopharmacology. 1998;18(6):470476.CrossRefGoogle ScholarPubMed
78.Sauerberg, P, Jeppesen, L, Olesen, PH, et al.Muscarinic agonists with antipsychotic-like activity: structure-activity relationships of 1,2,5-thiadiazole analogues with functional dopamine antagonist activity. J Med Chem. 1998;41(22):43784384.CrossRefGoogle ScholarPubMed
79.Shannon, HE, Rasmussen, K, Bymaster, Fet al.Xanomeline, an M1/M4 preferring muscarinic cholinergic receptor agonist, produces antipsychotic-like activity in rats and mice. Schizophr Res. 2000;42:249259.CrossRefGoogle Scholar
80.Sur, C, Mallorga, PJ, Wittmann, M, et al.N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates N-methyl-D-aspartate receptor activity. Proc Natl Acad Sci U S A. 2003;100(23):1367413679.CrossRefGoogle ScholarPubMed
81. Safety Study of ACP-104: To Demonstrate the Safety, Tolerability, and Pharmacokinetics. Available at: http://clinicaltrials.gov/ct2/show/NCT00628420?term=NCT00628420&rank=1. Accessed September 15, 2008.Google Scholar
82.Thal, LJ, Forrest, M, Loft, H, Mengel, H. Lu 25-109, a muscarinic agonist, fails to improve cognition in Alzheimer's disease. Neurology. 2000;54(2):421.CrossRefGoogle ScholarPubMed
83.Young, CD, Meltzer, HY, Deutch, AY. Effects of desmethylclozapine on fos protein expression in the forebrain: in vivo biological activity of the clozapine metabolite. Neuropsychopharmacogy. 1998;19(1):99103.CrossRefGoogle ScholarPubMed
84.Mirza, NR, Peters, D, Sparks, RG. Xanomeline and the antipsychotic potential of muscarinic receptor subtype selective agonists. CNS Drug Rev. 2003;9(2):159186.CrossRefGoogle ScholarPubMed
85.Jakubík, J, Michal, P, Machová, E, Doležal, V. Importance and prospects for design of selective muscarinic agonists. Physiol Res. 2008 May 13 [Epub ahead of print].Google Scholar
86.Shekhar, A, Potter, WZ, Lightfoot, J, et al.Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am J Psychiatry. 2008;165(8):10331039CrossRefGoogle Scholar
87.Burstein, ES, Ma, JN, Wong, S, et al.Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist. J Pharmacol Exp Ther. 2005;315(3):12781287.CrossRefGoogle ScholarPubMed
88.Natesan, S, Reckless, GE, Barlow, KB, Nobrega, JN, Kapur, S. of N-desmethylclozapine as a potential antipsychotic–preclinical studies. Neuropsychopharmacology. 2007;32(7):15401549.CrossRefGoogle ScholarPubMed
89.Lameh, J, Burstein, ES, Taylor, E, Weiner, DM, Vanover, KE, Bonhaus, DW. Pharmacology of N-desmethylclozapine. Pharmacol Ther. 2007;115(2):223231.CrossRefGoogle ScholarPubMed
38
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Muscarinic Agonists for the Treatment of Cognition in Schizophrenia
Available formats
×

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

Muscarinic Agonists for the Treatment of Cognition in Schizophrenia
Available formats
×

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

Muscarinic Agonists for the Treatment of Cognition in Schizophrenia
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *