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{{Short description|Activating agent of the muscarinic acetylcholine receptor}}
{{Infobox drug class
A '''muscarinic receptor agonist''' is an agent that activates the activity of the [[muscarinic acetylcholine receptor]]. The muscarinic receptor has different subtypes, labelled M1-M5, allowing for further differentiation.▼
| Name = Muscarinic agonist
| Image = Muscarine.svg
| Use =
| Caption = [[Skeletal formula|Skeletal structure formula]] of [[muscarine]]
| ATC_prefix = N07
| MeshID = D018721
▲A '''muscarinic
==Clinical significance==
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=== M1 ===
M1-type muscarinic [[acetylcholine]] receptors play a role in [[cognition|cognitive]] processing. In [[Alzheimer disease]] (AD), [[amyloid]] formation may decrease the ability of these receptors to transmit signals, leading to decreased cholinergic activity. As these receptors themselves appear relatively unchanged in the disease process, they have become a potential therapeutic target when trying to improve cognitive function in patients with AD.<ref>{{cite journal | vauthors = Fisher A, Brandeis R, Bar-Ner RH, Kliger-Spatz M, Natan N, Sonego H, Marcovitch I, Pittel Z
A number of muscarinic agonists have been developed and are under investigation to treat AD. These agents show promise as they are [[neurotrophin|neurotrophic]], decrease amyloid depositions, and improve damage due to [[oxidative stress]]. [[Tau protein|Tau]]-phosphorylation is decreased and cholinergic function enhanced. Notably several agents of the AF series of muscarinic agonists have become the focus of such research:. '''AF102B, AF150(S), AF267B'''. In animal models that are mimicking the damage of AD, these agents appear promising.
The agent [[xanomeline]] has been proposed as a potential treatment for [[schizophrenia]].<ref name="pmid18593778">{{cite journal |vauthors=Shekhar A, Potter WZ, Lightfoot J, etal |title=Selective Muscarinic Receptor Agonist Xanomeline as a Novel Treatment Approach for Schizophrenia |journal=Am J Psychiatry |volume= 165|issue= 8|pages= 1033–9|date=July 2008 |pmid=18593778 |doi=10.1176/appi.ajp.2008.06091591 |
=== M3 ===
In the form of [[pilocarpine]], muscarinic receptor agonists have been used medically for a short time.
* M3 agonists▼
** '''[[Aceclidine]]''', for glaucoma
▲*M3 agonists
** '''[[
** '''[[Pilocarpine]]''' is a drug that acts as a muscarinic receptor agonist that is used to treat [[glaucoma]]
** '''[[Cevimeline]]''' (AF102B) (Evoxac
▲** '''[[Pilocarpine]]''' is a drug that acts as a muscarinic receptor agonist that is used to treat [[glaucoma]].
▲** '''[[Cevimeline]]''' (AF102B) (Evoxac) is a muscarinic agonist that is an [[Food and Drug Administration]] (FDA)-[[approved drug]] and used for the management of dry mouth in [[Sjögren's syndrome]].
==Muscarinic versus nicotinic activity==
{| class="wikitable"
!colspan=5| Comparison of cholinergic agonists <ref name=Rang&Dale6thUnless>Unless else specified in boxes, then reference is: Table 10-3 in: {{cite book |author1=Rod Flower |author2=Humphrey P. Rang |author3=Maureen M. Dale |author4=Ritter, James M. |title=Rang & Dale's pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2007
|-▼
! rowspan="2" |Substance
! colspan="2" |Receptor specificity
! rowspan="2" |Hydrolysis by [[acetylcholinesterase]]
! rowspan="2" |Comments
|-
!Muscarinic
!Nicotinic
| Muscarinic || Nicotinic▼
|-
| [[Acetylcholine]] || +++ || +++ || +++ || Endogenous ligand
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| [[Carbachol]] || ++ || +++ || - || Used in the treatment of [[glaucoma]]
|-
| [[Methacholine]] || +++ || + || ++ || Used to diagnose [[bronchial hyperreactivity]],<ref name="pmid17565027">{{cite journal
|-
| [[Bethanechol]] || +++ || - || - || Used in bladder and gastrointestinal hypotonia.
|-
| [[Muscarine]] || +++ || - || - || Natural [[alkaloid]] found in certain mushrooms.
Cause of one form of mushroom poisoning |-
| [[Nicotine]] || - || +++ || - || Natural alkaloid found in the [[tobacco plant]].
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| [[Pilocarpine]] || ++ || - || - || Used in glaucoma.
|-
| [[Oxotremorine]] || ++ ||+<ref>{{Cite journal|title = Activation of muscle nicotinic acetylcholine receptor channels by nicotinic and muscarinic agonists|journal = British Journal of Pharmacology|date = 1999-12-01|issn = 0007-1188|pmc = 1571784|pmid = 10602325|pages = 1467–1476|volume = 128|issue = 7|doi = 10.1038/sj.bjp.0702941|
symptoms of [[Parkinson's disease]]. |}
== Muscarinic acetylcholine receptor subtypes ==
{{expand section|date=April 2019}}
The targets for muscarinic agonists are the muscarinic receptors: [[Muscarinic acetylcholine receptor M1|M<sub>1</sub>]], [[Muscarinic acetylcholine receptor M2|M<sub>2</sub>]], [[Muscarinic acetylcholine receptor M3|M<sub>3</sub>]], [[Muscarinic acetylcholine receptor M4|M<sub>4</sub>]] and [[Muscarinic acetylcholine receptor M5|M<sub>5</sub>]]. These receptors are [[GPCRs]] coupled to either [[Gi subunit|Gi]] or [[Gq subunits]].
▲|-
| [[Muscarinic acetylcholine receptor M1|M<sub>1</sub>]]▼
▲|}
== See also ==
* [[Muscarine]]▼
* [[Nicotinic acetylcholine receptor]]
* [[Nicotinic agonist]]
* [[Nicotinic antagonist]]
▲* [[Muscarinic acetylcholine receptor]]
▲* [[Muscarine]]
== References ==
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==External links==
* {{MeshName|Muscarinic+Agonists}}
{{Pharmacomodulation}}
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