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Titolo:
Treatment of cognitive dysfunction associated with Alzheimer's disease with cholinergic precursors. Ineffective treatments or inappropriate approaches?
Autore:
Amenta, F; Parnetti, L; Gallai, V; Wallin, A;
Indirizzi:
Univ Camerino, Dept Pharmacol Sci & Expt Med, Clin Res Unit, I-62032 Camerino, Italy Univ Camerino Camerino Italy I-62032 n Res Unit, I-62032 Camerino, Italy Univ Perugia, Dept Neurosci, I-06100 Perugia, Italy Univ Perugia PerugiaItaly I-06100 Dept Neurosci, I-06100 Perugia, Italy Gothenburg Univ, Sahlgrens Univ Hosp, Inst Clin Neurosci, Molndal, Sweden Gothenburg Univ Molndal Sweden osp, Inst Clin Neurosci, Molndal, Sweden
Titolo Testata:
MECHANISMS OF AGEING AND DEVELOPMENT
fascicolo: 16, volume: 122, anno: 2001,
pagine: 2025 - 2040
SICI:
0047-6374(200111)122:16<2025:TOCDAW>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
L-ALPHA-GLYCERYLPHOSPHORYLCHOLINE; CDP-CHOLINE; DOUBLE-BLIND; SENILE DEMENTIA; ACETYLCHOLINE-RELEASE; MUSCARINIC AGONISTS; MEMORY; BRAIN; PHOSPHATIDYLSERINE; LECITHIN;
Keywords:
Alzheimer's disease; cholinergic approach; cholinesterase inhibitors; cholinergic precursors; controlled clinical trials;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
85
Recensione:
Indirizzi per estratti:
Indirizzo: Amenta, F Univ Camerino, Dept Pharmacol Sci & Expt Med, Clin Res Unit, ViaScalzino 3, I-62032 Camerino, Italy Univ Camerino Via Scalzino 3 CamerinoItaly I-62032 rino, Italy
Citazione:
F. Amenta et al., "Treatment of cognitive dysfunction associated with Alzheimer's disease with cholinergic precursors. Ineffective treatments or inappropriate approaches?", MECH AGE D, 122(16), 2001, pp. 2025-2040

Abstract

The observations of the loss of cholinergic function in neocortex and hippocampus in Alzheimer's disease (AD) developed the hypothesis that replacement of cholinergic function may be of therapeutic benefit to AD patients. The different approaches proposed or tested included intervention with acetylcholine (ACh) precursors, stimulation of ACh release, use of muscarinic or nicotinic receptor agonists and acetylcholinesterase (AChE) or cholinesterase (ChE) inhibition. Inhibition of endogenous ACh degradation through ChE inhibitors and precursor loading were treatments more largely investigated in clinical trials. Of the numerous compounds in development for the treatment of AD, AChE and ChE inhibitors are the most clinically advanced, although clinical trials conducted to date did not always confirm a significant benefit of these drugs on all symptom domains of AD. The first attempts in the treatment of AD with cholinergic precursors did not confirm a clinical utility of this class of compounds in well controlled clinical trials. However, cholinergic precursors most largely used such as choline and phosphatidylcholine (lecithin) were probably not suitable for enhancing brain levels of ACh. Other phospholipids involved in choline biosynthetic pathways such as CDP-choline, choline alphoscerate and phosphatidylserine clearly enhancedACh availability or release and provided a modest improvement of cognitivedysfunction in AD, these effects being more pronounced with choline alphoscerate. Although some positive results cannot be generalized due to the small numbers of patients studied, they probably would justify reconsiderationof the most promising molecules in larger carefully controlled trials. (C)2001 Elsevier Science Ireland Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 12:17:33