The selective muscarinic agonist xanomeline improves both the cognitive deficits and behavioral symptoms of Alzheimer disease

Alzheimer Disease and Associated Disorders

Volumn 11, Issue SUPPL. 4, 1997, Pages

  Bodick, N C ^a   Offen, W W ^a   Shannon, H E ^a   Satterwhite, J ^a   Lucas, R ^a   Van Lier, R ^a   Paul, S M ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

Alzheimer disease; Behavior; Cognition; Muscarinic; Xanomeline

Indexed keywords

MUSCARINIC AGENT; XANOMELINE;

ADULT; AGED; AGITATION; ALZHEIMER DISEASE; ARTICLE; BEHAVIOR DISORDER; CLINICAL TRIAL; COGNITIVE DEFECT; COMPUTER ANALYSIS; CONTROLLED CLINICAL TRIAL; DELUSION; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; FEMALE; GASTROINTESTINAL SYMPTOM; HALLUCINATION; HUMAN; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RATING SCALE; SINGLE BLIND PROCEDURE; SYMPTOM; SYMPTOMATOLOGY;

ADMINISTRATION, ORAL; AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; BEHAVIORAL SYMPTOMS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; MIDDLE AGED; MUSCARINIC AGONISTS; NEUROBEHAVIORAL MANIFESTATIONS; NEUROPSYCHOLOGICAL TESTS; PSYCHOMETRICS; PSYCHOTROPIC DRUGS; PYRIDINES; THIADIAZOLES; TREATMENT OUTCOME;

EID: 0030686570     PISSN: 08930341     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (41)

1. Bartus RT, Dean RL, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982;217:408-17.
2. Bernard V, Normand E, Bloch B. Phenotypical characterization of the rat striatal neurons expressing muscarinic receptor genes. J Neurosci 1992;12:3591-600.
3. Bodick NC, DeLong AF, Bonate PL, Gillespie T, Henry DP, Satterwhite JH, Xanomeline, a specific m1 agonist: early clinical studies. In: Giacobini E, Becker R, eds. Alzheimer disease: therapeutic strategies. Boston: Birkhäuser, 1994:234-8.
4. Bodick NC, Offen WW, Levey AI, et al. Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer's disease. Arch Neurol 1997; 54:465-73.
5. Bonner TI, Buckley NJ, Young AC, Brann MR. Identification of a family of muscarinic acetylcholine receptor genes. Science 1987; 237:527-32.
6. Bymaster FP, Wong DT, Mitch CH, et al. Neurochemical effects of the m1 muscarinic agonist xanomeline (LY246708/NNC11-0232). J Pharmacol Exp Ther 1994;269:282-9.
7. Coyle JT, Price DL, DeLong MR. Alzheimer's disease: a disorder of cortical cholinergic innervation. Science 1983;219:1184-90.
8. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44: 2308-14.
9. Cutler NR, Sramek JJ, Seifert RD, et al. A bridging study of xanomeline tartrate in Alzheimer's disease (AD) [Abstract]. Biol Psychiatry 1994;35:628.
10. Davis KL, Thai LJ, Gamzu ER, et al. A double-blind, placebo-controlled multicentre study of tacrine for Alzheimer's disease. N Engl J Med 1992;327:1253-9.
11. DeLapp NW, Eckols K, Bymaster FP, Mitch CH, Shannon HE, Ward JS. The m1 agonist xanomeline potently stimulates APPs release from CHO-m1 cells. Life Sci 1995;56:1024.
12. Evans D, Funkenstein H, Albert M, et al. Prevalence of Alzheimer's disease in a community population of older persons. JAMA 1989; 262:2551-6.
13. Farde L, Suhara T, Halldin C, et al. New radioligands for PET-examination of central muscarinic receptors. Presented at: Alzheimer's and Parkinson's Diseases Recent Developments Third International Conference, Chicago, Nov. 1-6, 1993.
14. Farlow M, Gracon SI, Hershey LA, Lewis KW, Sadowsky CH, Dolan-Ureno J. A controlled trial of tacrine in Alzheimer's disease. JAMA 1992;268:2523-9.
15. Ferris SH, Steinberg G, Shulman E, et al. Institutionalization of Alzheimer's patients: reducing precipitating factors through family counseling [abstract]. Arch Found Thanatol 1985;12:7.
16. Flynn DD, Ferrari-DiLeo G, Mash DC, Levey AI. Differential regulation of molecular subtypes of muscarinic receptors in Alzheimer's disease. J Neurochem 1995;64:1888-91.
17. Folstein MF, Folstein SE, McHugh PR. "Mini-Mental State" - a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-98.
18. Giacobini E. Cholinergic receptors in human brain: effects of aging and Alzheimer's disease. J Neurosci Res 1990;27:548-60.
19. Gilley DW, Wilson RS, Bennett DA, Bernard BA, Fox JH. Predictors of behavioral disturbance in Alzheimer's disease. J Gerontol 1991; 46:362-71.
20. Growdon JH. Treatment for Alzheimer's disease? N Engl J Med 1992; 327:1306-8.
21. Katzman R. The prevalence and malignancy of Alzheimer's disease: a major killer. Arch Neurol 1976;33:217-8.
22. Knapp MJ, Knopman DS, Solomon PR, Pendlebury WW, Davis CS, Gracon SI. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. JAMA 1994;271:985-91.
23. Levey AI, Kitt CA, Simonds WF, Price DL, Brann MR. Identification and localization of muscarinic acetylcholine receptor proteins in brain with subtype-specific antibodies. J Neurosci 1991;11:3218-26.
24. Lorenzo A, Yankner BA. Beta-amyloid neurotoxicity requires fibril formation and is inhibited by Congo red. Proc Natl Acad Sci USA 1994;91:12243-7.
25. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939-44.
26. Mohs RC, Cohen L. Alzheimer's Disease Assessment Scale (ADAS). Psychopharmacol Bull 1988;24:627-8.
27. Mortimer JA, Ebbitt B, Jun S-P, Finch MD. Predictors of cognitive and functional progression in patients with probable Alzheimer's disease. Neurology 1992;42:1689-96.
28. Nitsch RM, Slack BE, Wurtman RJ, Growdon JH. Release of Alzheimer's amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science 1992;258:304-7.
29. Patterson MB, Bolger JP. Assessment of behavioral symptoms in Alzheimer disease. Alzheimer Dis Assoc Disord 1994;8:4-20.
30. Raskind MA, Peskind ER. Neurobiologic bases of noncognitive behavioral problems in Alzheimer disease. Alzheimer Dis Assoc Disord 1994;8(suppl 3):S54-60.
31. Reisberg B, Borenstein J, Franssen E, Shulman E, Steinberg G, Ferris SH. Remediable behavioral symptomatology in Alzheimer's disease. Hasp Comm Psychiatr 1986;37:1199-201.
32. Reisberg B, Borenstein J, Salob S, Ferris SH, Franssen E, Georgotas A. Behavioral symptoms in Alzheimer's disease: phenomenology and treatment. J Clin Psychiatry 1987;48(suppl 5):S9-15.
33. Rosen J, Zubenko GS. Emergence of psychosis and depression in the longitudinal evaluation of Alzheimer's disease. Biol Psychiatry 1991;29:224-32.
34. Selkoe DJ. Alzheimer's disease, a central role for amyloid. J Neuropathol Exp Neurol 1994;43:438-47.
35. Spiegel R, Brunner C, Ermini-Fünfschilling D, et al. A new behavioral assessment scale for geriatric out- and in-patients: the NOSGER (Nurse's Observation Scale for Geriatric Patients). J Am Geriatr Soc 1991;39:339-47.
36. Svensson AL, Alafuzoff I, Nordberg A. Characterization of muscarinic receptor subtypes in Alzheimer and control brain cortices by selective muscarinic antagonists. Brain Res 1992;596:142-8.
37. Teri L, Borson S, Kiyak HA, Yamagishi M. Behavioral disturbance, cognitive dysfunction, and functional skill - prevalence and relationship in Alzheimer's disease. J Am Geriatr Soc 1989;37:109-16.
38. Teri L, Rabins P, Whitehouse P, et al. Management of behavior disturbance in Alzheimer disease: current knowledge and future directions. Alzheimer Dis Assoc Disord 1992;6:77-88.
39. Wagner AW, Teri L, Orr-Rainey N. Behavior problems of residents with dementia in special care units. Alzheimer Dis Assoc Disord 1995;9:121-7.
40. Wragg RE, Jeste DV. Overview of depression and psychosis in Alzheimer's disease. Am J Psychiatry 1989;146:577-87.
41. Yasuda RP, Ciesla W, Flores LR, et al. Development of antisera selective for m4 and m5 muscarinic cholinergic receptors: distribution of m4 and m5 receptors in rat brain. Mol Pharmacol 1993;43: 149-57.