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Titolo:
Modulation of nicotinic receptor activity in the central nervous system: Anovel approach to the treatment of Alzheimer disease
Autore:
Albuquerque, EX; Santos, MD; Alkondon, M; Pereira, EFR; Maelicke, A;
Indirizzi:
Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 t Therapeut, Baltimore, MD 21201 USA Univ Fed Rio de Janeiro, Ctr Ciencias Saude, Inst Ciencias Biomed, Dept Farmacol Bas & Clin, Rio De Janeiro, Brazil Univ Fed Rio de Janeiro Rio De Janeiro Brazil n, Rio De Janeiro, Brazil Univ Mainz, Sch Med, Inst Physiol Chem & Pathobiochem, Mol Neurobiol Lab, D-6500 Mainz, Germany Univ Mainz Mainz Germany D-6500 Mol Neurobiol Lab, D-6500 Mainz, Germany
Titolo Testata:
ALZHEIMER DISEASE & ASSOCIATED DISORDERS
, volume: 15, anno: 2001, supplemento:, 1
pagine: S19 - S25
SICI:
0893-0341(200108)15:<S19:MONRAI>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; ACETYLCHOLINE-RECEPTORS; HIPPOCAMPAL-NEURONS; CHOLINERGIC HYPOTHESIS; SYNAPTIC TRANSMISSION; CA1 INTERNEURONS; CONTROLLED TRIAL; BINDING-SITES; MEMORY; GALANTAMINE;
Keywords:
Alzheimer disease; dual mechanism of action; allosteric modulation; nAChR; galantamine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Albuquerque, EX Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, 655 W Baltimore St, Baltimore, MD 21201 USA Univ Maryland 655 W Baltimore StBaltimore MD USA 21201 SA
Citazione:
E.X. Albuquerque et al., "Modulation of nicotinic receptor activity in the central nervous system: Anovel approach to the treatment of Alzheimer disease", ALZ DIS A D, 15, 2001, pp. S19-S25

Abstract

Impaired cholinergic function in the central nervous system is an early feature of Alzheimer disease (AD). Currently, cholinergic deficit is usually corrected by increasing the amount of acetylcholine in the synapse by inhibiting acetylcholinesterase (AChE). One of the most consistent cholinergic deficits in AD is the reduced expression of nicotinic acetylcholine receptors (nAChR) in the brain. Since these receptors are essential for learning and memory, restoring nicotinic cholinergic function is a promising approach to treating AD. Allosteric modulation of nAChR is a novel approach, which circumvents development of tolerance through long-term use of conventional nicotinic agonists. Allosteric modulators interact with receptor-binding sites distinct from those capable of recognizing the natural agonist. Positiveallosteric modulation of nAChR activity has no effect on conductance of single channels; instead, by facilitating channel opening, it potentiates responses evoked by the interaction of the natural agonist with presynaptic and postsynaptic nAChR. Allosteric modulation of nAChR activity could therefore potentially produce a significant benefit in AD. One such allosteric modulator is galantamine. In addition to increasing nAChR activity, galantamine also inhibits AChE. This novel, dual mechanism of action distinguishes galantamine from many other AChE inhibitors. Galantamine has been shown to improve cognitive and daily function for at least 6 months in placebo-controlled trials, and to maintain these functions at baseline levels for at least12 months in a 6-month open-label extension study. Galantamine has positive effects on nAChR expression, which are likely to contribute to its sustained efficacy in the treatment of AD patients.

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Documento generato il 18/02/20 alle ore 04:14:54