Imaging of muscarinic receptors in the central nervous system

Current Pharmaceutical Design

Volumn 12, Issue 30, 2006, Pages 3901-3913

  Eckelman, W C ^a  

^a Molecular Tracer LLC   (United States)

Author keywords

Acetylcholine; FP TZTP; HPLC MS; IQNB; Knock out mice; Muscarinic receptor

Indexed keywords

1 METHYL 4 PIPERIDYL BENZILATE C 11; 3 QUINUCLIDINYL 4 IODOBENZILATE I 123; ACETYLCHOLINE; ACETYLCHOLINESTERASE; APOLIPOPROTEIN E; ATROPINE; BENZATROPINE MESILATE C 11; BROMODEXETIMIDE BR 76; CLOZAPINE; DEXETIMIDE; DONEPEZIL; HALOTHANE; IODIDEXETIMIDE I 123; IODODEXETIMIDE I 123; MEPENZOLATE; MUSCARINIC RECEPTOR; N PROPYL 3 PIPERIDYL BENZILATE C 11; NEOSTIGMINE; NEUROTRANSMITTER; OLANZAPINE; OXYGEN 15; PHENSERINE; QUINUCLIDINYL BENZILATE; RADIOLIGAND; RISPERIDONE; SCOPOLAMINE BROMIDE C 11; SUXAMETHONIUM; TRACER; TROPANYL BENZILATE C 11; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ALZHEIMER DISEASE; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL STUDY; DRUG DESIGN; DRUG HALF LIFE; DRUG INFUSION; DRUG MECHANISM; DRUG MONITORING; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG TARGETING; GENETIC PREDISPOSITION; HUMAN; IMAGING SYSTEM; IN VIVO STUDY; LIGAND BINDING; NON INVASIVE MEASUREMENT; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; RECEPTOR AFFINITY; REVIEW; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; STRUCTURE ANALYSIS;

ANIMALS; CENTRAL NERVOUS SYSTEM; HUMANS; NERVOUS SYSTEM DISEASES; POSITRON-EMISSION TOMOGRAPHY; RADIOISOTOPES; RECEPTORS, MUSCARINIC; TOMOGRAPHY, EMISSION-COMPUTED, SINGLE-PHOTON;

EID: 33749858854     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161206778559678     Document Type: Review

References (108)

1. Eckelman WC. Radiolabeling with technetium-99m to study high-capacity and low-capacity biochemical systems. Eur J Nucl Med 1995; 22(3): 249-63.
2. Hevesy G, Paneth F. A Manual of Radioactivity. Second Edition. London: Oxford University Press 1938.
3. Kamen MD. Isotopic tracers in biology. New York, NY: Academic Press 1957.
4. 125I] iodobenzilate transport and specific binding to muscarinic acetylcholine receptor in rat brain in vivo. J Cereb Blood Flow Metabol 1990; 10: 781-807.
5. Blasberg RG. Receptor binding radiotracers: personal history of the past 20 years. Nucl Med Biol 2001; 28(5): 573-83.
6. Patlak CS, Blasberg RG. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations. J Cereb Blood Flow Metab 1985; 5(4): 584-90.
7. Wagner JG, Fundamentals of Clinical Pharmacokinetics. Hamilton, Ill.: Drug Intelligence, 1981.
8. Myers WG. Radioiodine- 125 in biomedicine: 1959-1984. J Nucl Med 1984; 25(12): 1389-1391.
9. Eckelman WC, Frank JA, Brechbiel M. Theory and practice of imaging saturable binding sites. Invest Radiol 2002; 37(3): 101-6.
10. Eckelman WC. Radiolabeled muscarinic radioligands for in vivo studies. Nucl Med Biol 2001; 28(5): 485-91.
11. Farrow JT, O'Brien RD. Binding of atropine and muscarone to rat brain fractions and its relation to the acetylcholine receptor. Mol Pharmacol 1973; 9(1): 33-40.
12. Synder SH, Chang KJ, Kuhar MJ, Yamamura HI. Biochemical identification of the mammalian muscarinic cholinergic receptor. Fed Proc 1975; 34(10): 1915-21.
13. Yamamura HI, Snyder SH. Muscarinic cholinergic binding in rat brain. Proc Natl Acad Sci USA 1974; 71(5): 1725-1729.
14. Eckelman WC. In: Eckelman WC, Ed. Radiolabeled adrenergic and muscarinic blockers for in vivo studies. Receptor Binding Radiotracers. CRC Press, Inc., 1982; 1: 69-91.
15. Eckelman WC, Reba RC, Rzeszotarski WJ, Gibson RE, Hill T, Holman BL, et al. External imaging of cerebral muscarinic acetylcholine receptors. Science 1984; 223: 291-293.
16. Wagner HN Jr, Burns HD, Dannals RF, Wong DF, Langstrom B, Duelfer T, et al. Imaging dopamine receptors in the human brain by positron tomography. Science 1983; 221(4617): 1264-6.
17. Zeeberg BR, Boulay SF, Gitler MS, Sood VK, Reba RC. Correction of the seterochemistry assignment of the benzilic acid center in ®-(-)-3-quinuclidinyl (S)-(-)-4-iodobenzilate [R,S)-4-IQNB]. Appl Radiat Isot 1997; 48: 463-467.
18. Kiesewetter DO, Silverton JV, Eckelman WC. Stereoselective synthesis of [R,R]IQNB and fluoroalkyl analogs of QNB. J Labelled Cpd Radiopharm 1994; 35: 419-421,
19. Ng JH, Hag LL. Streamlining drug discovery: finding the right drug against the right target to treat the right disease. Drug Discov Today 2004; 9: 59-60.
20. Goerres GW, Stupp R, Barghouth G, Hany TF, Pestalozzi B, Dizendorf E, et al. The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate. Eur J Nucl Med Mol Imaging 2005; 32(2): 153-62.
21. 11C]scopolamine and positron emission tomography. J Cereb Blood Flow Metab 1992; 12(1): 147-54.
22. 11C]tropanyl benzilate-binding to muscarinic cholinergic receptors: methodology and kinetic modeling alternatives. J Cereb Blood Flow Metab 1994; 14(1): 85-99.
23. 11C]NMPB and positron emission tomography: method development and differentiation of tracer delivery from receptor binding. J Cereb Blood Flow Metab 1998; 18(6): 619-31.
24. Piggott MA, Owens J, O'Brien J, Colloby S, Fenwick J, Wyper D, et al. Muscarinic receptors in basal ganglia in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease. J Chem Neuroanat 2003; 25(3): 161-73.
25. Nobuhara K, Farde L, Halldin C, Karlsson P, Swahn CG, Olsson H, et al. SPET imaging of central muscarinic acetylcholine receptors with iodine- 123 labelled E-IQNP and Z-IQNP. Eur J Nucl Med 2001; 28(1): 13-24.
26. 18F]FP-TZTP: control and competition studies. J Cereb Blood Flow Metab 1998; 18(10): 1130-42.
27. Holman BL, Gibson RE, Hill TC, Eckelman WC, Albert M, Reba RC. Muscarinic acetylcholine receptors in Alzheimer's disease. In vivo imaging with iodine 123-labeled 3-quinuclidinyl-4-iodobenzilate and emission tomography. JAMA 1985; 254(21): 3063-6.
28. 11C-methyl]-benztropine. Synapse 1990; 5(3): 213-23.
29. Weinberger DR, Mann U, Gibson RE, Coppola R, Jones DW, Braun AR, et al. Cerebral muscarinic receptors in primary degenerative dementia as evaluated by SPECT with iodine-123-labeled QNB. Adv Neurol 1990; 51: 147-50.
30. 123IQNB and single photon emission computed tomography. Arch Neurol 1991; 48(2): 169-76.
31. Weinberger DR, Jones D, Reba RC, Mann U, Coppola R, Gibson R, et al. A comparison of FDG PET and IQNB SPECT in normal subjects and in patients with dementia. J Neuropsychiatry Clin Neurosci 1992; 4(3): 239-48.
32. Wyper DJ, Brown D, Patterson J, Owens J, Hunter R, Teasdale E, et al. Deficits in iodine-labelled 3-quinuclidinyl benzilate binding in relation to cerebral blood flow in patients with Alzheimer's disease. Eur J Nucl Med 1993; 20(5): 379-86.
33. Muller-Gartner HW, Mayberg HS, Fisher RS, Lesser RP, Wilson AA, Ravert HT, et al. Decreased hippocampal muscarinic cholinergic receptor binding measured by 123I-iododexetimide and single-photon emission computed tomography in epilepsy. Ann Neurol 1993; 34(2): 235-8.
34. Sunderland T, Esposito G, Molchan SE, Coppola R, Jones DW, Gorey J, et al. Differential cholinergic regulation in Alzheimer's patients compared to controls following chronic blockade with scopolamine: a SPECT study. Psychopharmacology (Berl) 1995; 121(2): 231-41.
35. Boundy KL, Rowe CC, Black AB, Kitchener MI, Barnden LR, Sebben R, et al. Localization of temporal lobe epileptic foci with iodine-123 iododexetimide cholinergic neuroreceptor single-photon emission computed tomography. Neurology 1996; 47(4): 1015-20.
36. 11C]tropany1 benzilate. J Cereb Blood Flow Metab 1996; 16(2): 303-10.
37. Claus JJ, Dubois EA, Booij J, Habraken J, de Munck JC, van Herk M, et al. Demonstration of a reduction in muscarinic receptor binding in early Alzheimer's disease using iodine-123 dexetimide single-photon emission tomography. Eur J Nucl Med 1997; 24(6): 602-8.
38. Sudo Y, Suhara T, Honda Y, Nakajima T, Okubo Y, Suzuki K, et al. Muscarinic cholinergic receptors in human narcolepsy: a PET study. Neurology 1998; 51(5): 1297-302.
39. 11C-N-methyl-4-piperidyl benzilate - comparison with cerebral blood flow and cerebral glucose metabolism. Ann Nucl Med 1998; 12(1): 35-42.
40. Asahina M, Suhara T, Shinotoh H, Inoue O, Suzuki K, Hattori T. Brain muscarinic receptors in progressive supranuclear palsy and Parkinson's disease: a positron emission tomographic study. J Neurol Neurosurg Psychiatry 1998; 65(2): 155-63.
41. 76Br]4-bromodexetimide. J Nucl Med 1999; 40(6): 935-41.
42. Yoshida T, Kuwabara Y, Sasaki M, Fukumura T, Ichimiya A, Takita M, et al. Sex-related differences in the muscarinic acetylcholinergic receptor in the healthy human brain - a positron emission tomography study. Ann Nucl Med 2000; 14(2): 97-101.
43. Raedler TJ, Knable MB, Jones DW, Lafargue T, Urbina RA, Egan MF, et al. In vivo olanzapine occupancy of muscarinic acetylcholine receptors in patients with schizophrenia. Neuropsychopharmacology 2000; 23(1): 56-68.
44. 123I]-IDEX SPECT study. Psychopharmacology (Berl) 2001; 156(1): 53-7.
45. Tsukada H, Kakiuchi T, Nishiyama S, Ohba H, Sato K, Harada N, et al. Age differences in muscarinic cholinergic receptors assayed with (+)N-[(11)C]methyl-3-piperidyl benzilate in the brains of conscious monkeys. Synapse 2001; 41(3): 248-57.
46. 11C]methyl-4-piperidyl benzilate combined with cerebral blood flow measurement in conscious monkeys. Brain Res 2001; 916(1-2): 22-31.
47. Zhao L, Yamashima T, Wang XD, Tonchev AB, Yamashita J, Kakiuchi T, et al. PET imaging of ischemic neuronal death in the hippocampus of living monkeys. Hippocampus 2002; 12(2): 109-18.
48. 11C]methyl-3-pyrrolidyl benzilate, a high-affinity reversible radioligand for PET studies of the muscarinic acetylcholine receptor. Synapse 2002; 45(1): 31-7.
49. Raedler TJ, Knable MB, Jones DW, Urbina RA, Egan MF, Weinberger DR. Central muscarinic acetylcholine receptor availability in patients treated with clozapine. Neuropsychopharmacology 2003; 28(8): 1531-7.
50. Kemp PM, Holmes C, Hoffmann S, Wilkinson S, Zivanovic M, Thom J, et al. A randomised placebo controlled study to assess the effects of cholinergic treatment on muscarinic receptors in Alzheimer's disease. J Neurol Neurosurg Psychiatry 2003; 74(11): 1567-70.
51. Benson BE, Carson RE, Kiesewetter DO, Herscovitch P, Eckelman WC, Post RM, et al. A potential cholinergic mechanism of procaine's limbic activation. Neuropsychopharmacology 2004; 29(7): 1239-50.
52. 11C-methyl]-benztropine and application to studies of propofol-induced unconsciousness in healthy human volunteers. Synapse 2004; 51(2): 91-101.
53. Podruchny TA, Connolly C, Bokde A, Herscovitch P, Eckelman WC, Kiesewetter DO, et al. In vivo muscarinic 2 receptor imaging in cognitively normal young and older volunteers. Synapse 2003; 48(1): 39-44.
54. Cohen RM, Podruchny TA, Bokde AL, Carson RE, Herscovitch P, Kiesewetter DO, et al. Higher in vivo muscarinic-2 receptor distribution volumes in aging subjects with an apolipoprotein E-epsilon4 allele. Synapse 2003: 49(3): 150-6.
55. Maziere M. Cholinergic neurotransmission studied in vivo using positron emission tomography of single photon emission computerized tomography. Pharmacol Ther 1995; 66(1): 83-101.
56. Freo U, Pizzolato G, Dam M, Ori C, Battistin L. A short review of cognitive and functional neuroimaging studies of cholinergic drugs: implications for therapeutic potentials. J Neural Transm 2002; 109(5-6): 857-70.
57. 18F]fluoronochloroepibatidine in rodent and human brain. Nucl Med Biol 1998; 25(5): 449-54.
58. 18F]Fluoro-A-85380, an in vivo tracer for the nicotinic acetylcholine receptors. Nucl Med Biol 1998; 25(7): 599-603.
59. Kuhl DE, Koeppe RA, Minoshima S, Snyder SE, Ficaro EP, Foster N, et al. In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease. Neurology 1999; 52: 691-699.
60. 11C]PMP). Synapse 1996; 22(2): 123-31.
61. Namba H, Irie T, Fukushi K, Iyo M. In vivo measurement of acetylcholinesterase activity in the brain with a radioactive acetylcholine analog. Brain Res 1994; 667: 278-282.
62. Tavitian B, Pappata S, Planas AM, Jobert A, Bonnot-Lours S, Crouzel C, et al. In vivo visualization of acetylcholinesterase with positron emission tomography. Neuroreport 1993; 4: 535-538.
63. Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, et al. Functional brain abnormalities in young adults at genetic risk for late-onset alzheimer's dementia. Proc Natl Acad Sci USA 2004; 101(1): 284-9.
64. St. George-Hyslop P. Molecular genetics of a1zheimer's disease. Biol Psychiatary 2000; 47: 183-199.
65. Wang Y, Klunk WE, Debnath ML, Huang GF, Holt DP, Shao L, et al. Development of a PET/SPECT agent for amyloid imaging in Alzheimer's disease. J Mol Neurosci 2004; 24(1): 55-62.
66. Quirion R, Aubert I, Labchak PA, Schaum RP, Teolis S, Gauthier S, et al. Muscarinic receptor subypes in human neurodegenerative disorders; focus on Alzheimer's disease. Trends Pharmacol Sci 1989; (Suppl): 80-84.
67. Aubert I, Araujo DM, Cecyre D, Robitaille Y, Gauthier S, Quirion R. Comparative alterations of nicotinic and muscarinic binding sites in Alzheimer's and Parkinson's diseases. J Neurochem 1992; 58(2): 529-541.
68. Rodriguez-Puertas R, Pascual J, Vilaro T, Pazos A. Autoradiographic distribution of M1, M2, M3 and M4 muscarinic receptor subtypes in Alzheimer's disease. Synapse 1997; 26: 341-350.
69. Doods H, Entzeroth M, Ziegler H, Schiavi G, Engel W, Mihm G, et al. Characterization of BIBN 99: a lipophilic and selective muscarinic M2 receptor antagonist. Eur J Pharmacol 1993; 242: 23-30.
70. McPherson DW, DeHaven-Hudkins DL, Callahan AP, Knapp FF Jr. Synthesis and biodistribution of iodine-125-labeled 1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate. A new ligand for the potential imaging of muscarinic receptors by single photon emission computed tomography. J Med Chem 1993; 36: 848-854.
71. McPherson DW, Lambert CR, Jahn K, Sood V, McRee RC, Zeeberg, B, et al. Resolution and in vitro and initial in vivo evaluation of isomers of iodine-125-labeled 1-azabicyclo[2.2.2]oct-3-yl alpha- hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate: a high-affinity ligand for the muscarinic receptor. J Med Chem 1995; 38: 3908-3917.
72. Herschberg BT, Mosser VA, Peterson GL, Toumadje A, Vogel WK, Johnson WC Jr, et al. Kinetic and biophysical analysis of the m2 muscarinic receptors. Life Sci 1995; 56: 907-913.
73. Boulay SF, Kiesewetter DO, Sood VK, Rayeq MR, Zeeberg BR, Eckelman WC. Autoradiographic evidence that (R)-3-quinuclidinyl (S)-4-fluoromethylbenzilate ((R,S)-FMeQNB) displays In vivo selectivity for the muscarinic m2 subtype. Nucl Med Biol 1996; 23: 889-896.
74. 18F]fluoromethyl QNB. Bioorg Med Chem 1997; 5: 1555-1567.
75. Kiesewetter DO, Lee JT, Park SG, Paik CH, Eckelman WC. Synthesis and biological properties of chiral fluoroaklyl quinuclidinyl benzilates. J Med Chem 1995; 38: 1711-1719.
76. Lee JT, Paik CH, Kiesewetter DO, Park SG, Eckelman WC. Evaluation of steroisomers of 4-fluoroalkyl analogs of 3-quinuclidinyl benzilate in in vivo competition study for muscarinic receptor subtypes, the M1, M2, and M3. Nucl Med Biol 1995; 22: 773-782.
77. Sauerberg P, Olesen PH, Nielsen S, Treppendahl S, Sheardown MJ, Honore T, et al. Novel functional M1 selective muscarinic agonists. Synthesis and structure-activity relationships of 3-(1,2,5-thiadiazoyl) -1,2,5,6-tetrahydro-1-methylpyridines. J Med Chem 1992; 2274-2283.
78. 11C]butylthio-TZTP in monkey and man. Dementia 1996; 7: 187-195.
79. Kiesewetter DO, Carson RE, Jagoda EM, Herscovitch P, Eckelman WC. In vivo muscarinic binding of 3-(alkylthio)-3-thiadiazolyl tetrahydropyridines. Synapse 1999, 31: 29-40.
80. 18F]FP-TZTP binding by loading doses of muscarinic agonists P-TZTP or FP-TZTP in vivo is not due to agonist-induced reduction in cerebral blood flow. Synapse 2003; 50(2): 151-63.
81. 18F]FP-TZTP, is greatly decreased in M2 receptor knockout mice but not in M1, M3 and M4 receptor knockout mice. Neuropharmacology 2003; 44(5): 653-61.
82. Eckelman WC. The use of gene-manipulated mice in the validation of receptor binding radiotracer. Nucl Med Biol 2003; 30(8): 851-60.
83. Eckelman WC. The use of PET and knockout mice in the drug discovery process. Drug Discov Today 2003; 8(9): 404-10.
84. Ring BJ, Wrighton SA, Aldridge SL, Hansen K, Haehner B, Shipley LA. Flavin-containing monooxygenase- mediated N-oxidation of the M(1)-muscarinic agonist xanomeline. Drug Metab Dispos 1999; 27: 1099-1103.
85. Andersen JV, Hansen KT. Normal-phase liquid chromatography-particle-beam mass spectrometry in drug metabolism studies of the dopamine receptor antagonist Odapipam and the muscarine M1 receptor agonist Xanomeline. Xenobiotica 1997; 27: 901-912.
86. Brown TJ, Shipley LA. Determination of xanomeline (LY246708 tartrate), an investigational agent for the treatment of Alzheimer's disease, in rat and monkey plasma by capillary gas chromatography with nitrogen-phosphorus detection. J Chromatogr B Analyt Technol Biomed Life Sci 1995; 665: 337-344.
87. Christensen EB, Andersen JB, Pedersen H, Jensen KG. Metabolites of [(14)C]-5-(2-ethyl-2H-tetrazol-5-yl)-1-methyl-1,2,3, 6-tetrahydropyridine in mice, rats, dogs, and humans. Drug Metab Dispos 1999; 27: 1341-1349.
88. Ma Y, Kiesewetter DO, Lang L, Eckelman WC. Application of LC-MS to the Analysis of New Radiopharmaceuticals. Mol Imaging Biol 2003; 5: 307-403.
89. Dichino DD, Welch MJ, Kilbourn MR, Raichle ME. Relationship between lipophilicity and brain extraction of C-11 labeled radio-pharmaceuticals. J Nucl Med 1983; 24: 1030-1038.
90. Logan J. A review of graphical methods for tracer studies and strategies to reduce bias. Nucl Med Biol 2003; 30(8): 833-44.
91. Carlsson A, Hansson LO, Waters N, Carlsson ML. Neurotransmitter aberrations in schizophrenia: new perspectives and therapeutic implications. Life Sci 1997; 61: 75-94.
92. Carlsson A, On the neuronal circuitries and neurotransmitters involved in the control of locomotor activity. J Neural Transm 1993; 40: 1-12.
93. Imperato A, Obinu MC, Gessa GL, Stimulation of both dopamine D1 and D2 receptors facilitates in vivo acetylcholine release in the hippocampus. Brain Res 1993; 618: 341-345.
94. Schloesser R, Simkowitz P, Bartlett EJ, Wolkin A, Smith GS, Dewey SL, et al. The study of neurotransmitter interactions using positron emission tomography and functional coupling. Clin Neuropharmacol 1996; 19: 371-389.
95. Laruelle M. Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cerebral Blood Flow Metabol 2000; 20: 423-451.
96. 11C]L-deprenyl in living baboon brain. J Neurochem 1988; 51: 1524-1534.
97. Vera DR, Woodle ES, Stadalnik RC, Kinetic sensitivity of a receptor binding radiopharmaceutical: Technetium-99m galactosyl-neoglycoalbumin. J Nucl Med 1989, 30: 1519-1530.
98. Eckelman WC, Sensitivity of new radiopharmaceuticals. Nucl Med Biol 1998; 25: 169-174.
99. Vera DR, Eckelman WC. Receptor 1980 and Receptor 2000: twenty years of progress in receptor-binding radiotracers. Nucl Med Biol 2001; 28(5): 475-6.
100. Skaddan MB, Kilbourn MR, Snyder SE, Sherman PS, Desmond TJ, Frey KA. Synthesis, (18)F-labeling, and biological evaluation of piperidyl and pyrrolidyl benzilates as in vivo ligands for muscarinic acetylcholine receptors. J Med Chem 2000; 43(23): 4552-62.
101. 18F]fluoroethyl)-4-piperidyl benzilate binding to muscarinic acetylcholine receptors. J Cereb Blood Flow Metab 2001; 21(2): 144-8.
102. 11C]NMPYB) to endogenous acetylcholine: PET imaging vs. tissue sampling methods. Nucl Med Biol 2004; 31(4): 393-7.
103. Eckelman WC. In: Bailey DL, Townsend DW, Valk PE, Maisey MN, Eds. The Use of Positron Emission Tomography (PET) in Drug Discovery and Development. Positron Emission Tomography: Principles & Practice. Springer-Verlag (London) Ltd., 2003.
104. Tsukada H, Nishiyama S, Fukumoto D, Ohba H, Sato K, Harada N. Effects of acute acetylcholinesterase inhibition on the cerebral cholinergic neuronal system and cognitive function: Functional imaging of the conscious monkey brain using animal PET in combination with microdialysis. Synapse 2004; 52: 1-10.
105. Brown D, Chisholm JA, Owens J, Pimlott S, Patterson J, Wyper D. Acetylcholine muscarinic receptors and response to anti-cholinesterase therapy in patients with Alzheimer's disease. Eur J Nucl Med Mol Imaging 2003; 30(2): 296-300.
106. Clader JW, Wang Y. Muscarinic receptor agonists and antagonists in the treatment of Alzheimer's disease. Curr Pharm Des 2005; 11(26): 3353-61.
107. Lahiri DK, Rogers JT, Greig NH, Sambamurti K. Rationale for the development of cholinesterase inhibitors as anti-Alzheimer agents. Curr Pharm Des 2004; 10(25): 3111-9.
108. Messer WS Jr. Bivalent ligands for G protein-coupled receptors. Curr Pharm Des 2004; 10(17): 2015-20.