Importance and prospects for design of selective muscarinic agonists

Title:

Importance and prospects for design of selective muscarinic agonists

Creator:

Jakubík, Jan, Michal, P., Eva Machová, and Vladimír Doležal

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:55035cbf-8bfb-45a0-8e13-8c7f3870be0d
uuid:55035cbf-8bfb-45a0-8e13-8c7f3870be0d
issn:0862-8408

Subject:

Fyziologie člověka a srovnávací fyziologie, neurochemie, fyziologie, neurochemistry, physiology, cholinergic transmission, xanomeline, muscarinic receptor subtypes, G-protein activation, ectopic agonists, 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

There are five subtypes of muscarinic receptors that serve various important physiological functions in the central nervous system and the periphery. Mental functions like attention, learning, and memory are attributed to the muscarinic M1 subtype. These functions decline during natural aging and an early deficit is typical for Alzheimer´s disease. In addition, stimulation of the M1 receptor increases non-amyloidogenic processing of the amyloid precursor protein and thus prevents accumulation of noxious β-amyloid fragments. The selectivity of classical muscarinic agonists among receptor subtypes is very low due to the highly conserved nature of the orthosteric binding site among receptor subtypes. Herein we summarize some recent studies with the functionally-selective M1 agonist xanomeline that indicate complex pharmacological profile of this drug that includes interactions with and activation of receptor from both orthosteric and ectopic binding sites, and the time-dependent changes of ligand binding and receptor activation. These findings point to potential profitability of exploitation of ectopic ligands in the search for truly selectiev muscarinic receptor agonists., J. Jakubík, P. Michal, E. Machová, V. Doležal., and Obsahuje bibliografii a bibliografické odkazy

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2008 Volume:57 | Number:Suppl 3

Harvested from:

CDK

Metadata only:

false