Muscarinic M1 receptor agonists: can they improve cognitive performance?

Muscarinic M1 receptor agonists: can they improve cognitive performance?

Due to their potential roles in the pathophysiologies of a number of central nervous system disorders such as depression (Dilsaver, 1986), schizophrenia (Raedler et al. 2006), Alzheimer’s disease (Araujo et al. 1988) and Parkinson’s disease (Ruberg et al. 1982), modulation of the muscarinic system has been a focus of drug discovery for decades. Particular attention has been paid to developing l...

Muscarinic Receptor Agonists and Antagonists

A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthes...

Contrasting effects of allosteric and orthosteric agonists on m1 muscarinic acetylcholine receptor internalization and down-regulation.

A new class of subtype-selective muscarinic acetylcholine (mACh) receptor agonist that activates the receptor through interaction at a site distinct from the orthosteric acetylcholine binding site has been reported recently. Here, we have compared the effects of orthosteric (oxotremorine-M, arecoline, pilocarpine) and allosteric [4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl] piperidine (AC-42)...

FRET-Based Detection of M1 Muscarinic Acetylcholine Receptor Activation by Orthosteric and Allosteric Agonists

BACKGROUND AND OBJECTIVE Muscarinic acetylcholine receptors (mAChRs) are 7-transmembrane, G protein-coupled receptors that regulate a variety of physiological processes and represent potentially important targets for therapeutic intervention. mAChRs can be stimulated by full and partial orthosteric and allosteric agonists, however the relative abilities of such ligands to induce conformational ...

Potentiation of the M1 muscarinic acetylcholine receptor signalling pathway achieved by novel allosteric agonists