The selective muscarinic agonist xanomeline improves both the cognitive deficits and behavioral symptoms of Alzheimer disease
| Autor: | N C, Bodick, W W, Offen, H E, Shannon, J, Satterwhite, R, Lucas, R, van Lier, S M, Paul |
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| Rok vydání: | 1997 |
| Předmět: |
Aged
80 and over Male Psychotropic Drugs Dose-Response Relationship Drug Psychometrics Pyridines Administration Oral Behavioral Symptoms Middle Aged Muscarinic Agonists Neuropsychological Tests Neurobehavioral Manifestations Treatment Outcome Double-Blind Method Alzheimer Disease Thiadiazoles Humans Female Aged |
| Zdroj: | Alzheimer disease and associated disorders. 11 |
| ISSN: | 0893-0341 |
| Popis: | The therapeutic effects of selective cholinergic replacement using oral xanomeline, an m1/m4 receptor agonist, were assessed in a multicenter study of 343 patients with Alzheimer disease (AD). Patients were randomized to parallel treatment arms (placebo, 25, 50, and 75 mg t.i.d. xanomeline) and followed through 6 months of double-blind therapy and 1 month of single-blind placebo washout. Completer analysis, using the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), revealed a significant treatment effect (75 mg t.i.d. vs. placebo; p = 0.045). Similar assessment of global status, using the Clinician's Interview-Based Impression of Change, was also significant (75 mg t.i.d. vs. placebo; p = 0.022). Treatment Emergent Signs and Symptoms analysis of the Alzheimer's Disease Symptomatology Scale, revealed highly significant (por = 0.002) dose-dependent reductions in vocal outbursts, suspiciousness, delusions, agitation, and hallucinations. On end-point analysis, the Nurses' Observational Scale for Geriatric Patients also showed a significant dose-response relationship (p = 0.018). The improvement in ADAS-Cog provides the first clinical evidence of involvement of the m1 muscarinic receptor in cognition. Furthermore, the favorable effects of xanomeline on disturbing behaviors suggest a novel approach for treatment of the noncognitive symptoms of AD. Although adverse effects (mainly gastrointestinal) associated with the oral formulation appear to limit its use, a large-scale study investigating the safety and efficacy of transdermal xanomeline is under way. |
| Databáze: | OpenAIRE |
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