Muscarinic receptor agonists and antagonists

Abstract

Although four different subtypes of the muscarinic acetylcholine (ACh) receptor with functional correlates are known to exist (function for M5 is still unclear), all muscarinic agonists and antagonists in clinical practice only show very weak selectivity. Therefore, intensive investigations are in progress to develop subtype selective ligands. This review describes the first M1 agonists and antagonists of the presynaptic M2 receptor, which can be used in the treatment of Alzheimer's disease (AD), and M3 antagonists, which will be useful in the treatment of urinary urge incontinence. In addition, muscarinic agonists were found to exhibit analgesic effects and M4 antagonists may be useful in the treatment of movement disorders. However, the latter two pharmacological findings will need more research work to become established in clinical trials.

[General Articles] Muscarinic and Nicotinic Cholinergic Agonists: Structural Analogies and Discrepancies

“…[2][3][4][5]. These compounds are able to adopt the pharmacophore conformation, but possess a substituent that may either block a heteroatom, or interact sterically with the binding site during the binding process.…”

“…Although at least five different subtypes of the muscarinic acetylcholine receptor exist, all muscarinic agonists and antagonists show only weak or no subtype selectivity [2]. The X-ray structure of muscarinic receptors are not yet known; the best template for modelling studies in this receptor family is the photoreceptor rhodopsin, the three dimensional structure of which [3,4] and the ligand binding domain of the metabotropic glutamate receptor [5] have been determined recently.…”

Analysis of spatiotemporal pattern and quantification of gastrointestinal slow waves caused by anticholinergic drugs

“…Anticholinergic drugs are known to have negative input to both the parasympathetic nervous system and the enteric nervous system, by blocking cholinergic neurotransmission. 47,48 By treating the intestine with these drugs and measuring the rhythmic contractions driven by ICC, we examine whether there is a link between enteric neurons and ICC.…”

Effect of the ortho-hydroxy group of salicylaldehyde in the A3 coupling reaction: A metal-catalyst-free synthesis of propargylamine

“…Propargylamines are important synthetic intermediates for the preparation of natural products [1], potential therapeutic agents [2], oxotremorine analogues [3] and multifunctional amino derivatives [4–5]. Compounds like resagiline or selegiline (structures 1 and 2 , Scheme 1) bearing a propargylamine moiety, are familiar as potent selective, irreversible monoamine oxidase (MAO) type B inhibitors [6] often used for the treatment of neuropsychiatric disorders such as Alzheimer’s and Parkinson diseases.…”