Importance and prospects for design of selective muscarinic agonists.
نویسندگان
چکیده
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 beta-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 selective muscarinic receptor agonists.
منابع مشابه
Title : Attenuation of cocaine ’ s reinforcing and discriminative stimulus effects via muscarinic M 1 acetylcholine receptor stimulation
Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine’s abuse-related effects. Here we sought to confirm and extend in the mouse species findings that nonselective muscarinic receptor antagonists can enhance cocaine’s discriminative stimulus. More importantly, we tested the hypothesis that muscarinic receptor agonists with varied receptor s...
متن کاملTitle : Attenuation of cocaine ’ s reinforcing and discriminative stimulus
Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine’s abuse-related effects. Here we sought to confirm and extend in the mouse species findings that nonselective muscarinic receptor antagonists can enhance cocaine’s discriminative stimulus. More importantly, we tested the hypothesis that muscarinic receptor agonists with varied receptor s...
متن کاملMicrosoft Word - 39700264-file00
Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine’s abuse-related effects. Here we sought to confirm and extend in the mouse species findings that nonselective muscarinic receptor antagonists can enhance cocaine’s discriminative stimulus. More importantly, we tested the hypothesis that muscarinic receptor agonists with varied receptor s...
متن کاملJPET Fast
Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine’s abuse-related effects. Here we sought to confirm and extend in the mouse species findings that nonselective muscarinic receptor antagonists can enhance cocaine’s discriminative stimulus. More importantly, we tested the hypothesis that muscarinic receptor agonists with varied receptor s...
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It has been revealed that dopamine (DA) modulates gastro-duodenal responses to stress. Several investigations have been made to identify the mechanisms and/or receptors by which DA or its promoters exert their gastroprotective function against stress, however there are many discrepancies in this respect. In order to clarify the relative contribution and/or interaction of two DA receptor subty...
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عنوان ژورنال:
- Physiological research
دوره 57 Suppl 3 شماره
صفحات -
تاریخ انتشار 2008