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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Muscarinic Receptor Agonists and Antagonists in the Treatment of Alzheimers Disease

Author(s): J. W. Clader and Y. Wang

Volume 11, Issue 26, 2005

Page: [3353 - 3361] Pages: 9

DOI: 10.2174/138161205774370762

Price: $65

Abstract

One of the consistent findings in the brains of Alzheimers Disease (AD) patients is loss of cholinergic function. The cholinergic approach to treatment of AD involves counteracting this loss in cholinergic activity by pharmacological intervention to increase cholinergic transmission. The cognitive effects of acetylcholine are mediated via the muscarinic M1 receptor. Direct stimulation of this receptor using muscarinic M1 agonists improves cognition in animal models and improves performance in cognitive tests in Alzheimers patients. Alternatively, antagonists of central presynaptic M2 receptors improves cognition by increasing the central release of acetylcholine. Both approaches require high selectivity for one muscarinic receptor sub-type both for efficacy and to avoid cholinergic side effects. In this review summarizes recent progress in the identification and characterization of selective muscarinic receptor ligands for the treatment of Alzheimers disease.

Keywords: alzheimers disease, cognition, muscarinic receptor


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