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((Short description|Substance that mimics stimulation of cholinergic receptors))
((more citations needed|date=December 2013))
A '''parasympathomimetic drug''', sometimes called a '''cholinomimetic drug'''<ref name="Dowd 2017"/> or '''[[cholinergic receptor]] [[agonist|stimulating agent]]''',<ref name="Forrester Dick McMenamin Roberts 2016 pp. 338–369.e1"/> is a substance that stimulates the [[parasympathetic nervous system]] (PSNS).<ref name="urlDorlands Medical Dictionary:parasympathomimetic">((cite web |url=http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp?pg=/ppdocs/us/common/dorlands/dorland/six/000078652.htm |title=Dorlands Medical Dictionary:parasympathomimetic |archive-url=https://web.archive.org/web/20090726174225/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp?pg=%2Fppdocs%2Fus%2Fcommon%2Fdorlands%2Fdorland%2Fsix%2F000078652.htm |archive-date=2009-07-26 |url-status=dead ))</ref><ref name="Forrester Dick McMenamin Roberts 2016 pp. 338–369.e1">((cite book | last1=Forrester | first1=John V. | last2=Dick | first2=Andrew D. | last3=McMenamin | first3=Paul G. | last4=Roberts | first4=Fiona | last5=Pearlman | first5=Eric | title=The Eye | chapter=General and ocular pharmacology | publisher=Elsevier | year=2016 | isbn=978-0-7020-5554-6 | doi=10.1016/b978-0-7020-5554-6.00006-x | pages=338–369.e1 | quote=Parasympathomimetics are a group of drugs that act either by directly stimulating the muscarinic receptor, for example pilocarpine, or by inhibiting the enzyme acetylcholinesterase, which hydrolyses the acetylcholine in the synapse.))</ref> These chemicals are also called '''[[cholinergic]] drugs''' because [[acetylcholine]] (ACh) is the [[neurotransmitter]] used by the PSNS.<ref name="Dowd 2017">((cite book | last=Dowd | first=Frank | title=Pharmacology and therapeutics for dentistry: Chapter 6 - Cholinergic Agonists and Muscarinic Receptor Antagonists | publisher=Elsevier | publication-place=St. Louis, Missouri | year=2017 | isbn=978-0-323-39307-2 | oclc=958121223 | pages=82–97 ))</ref><ref>[https://www.ncbi.nlm.nih.gov/mesh/68010277 Parasympathomimetics]</ref> Chemicals in this family can act either directly by stimulating the [[nicotinic acetylcholine receptor|nicotinic]] or [[muscarinic acetylcholine receptor|muscarinic]] receptors (thus mimicking acetylcholine), or indirectly by inhibiting [[cholinesterase]], promoting acetylcholine release, or other mechanisms.<ref>Brenner, G. M. (2000). ''Pharmacology.'' Philadelphia, PA: W.B. Saunders Company. ((ISBN|0-7216-7757-6))</ref> Common uses of parasympathomimetics include [[glaucoma]], [[Sjögren syndrome]] and [[underactive bladder]].<ref>((Cite journal|last1=Moro|first1=Christian|last2=Phelps|first2=Charlotte|last3=Veer|first3=Vineesha|last4=Clark|first4=Justin|last5=Glasziou|first5=Paul|last6=Tikkinen|first6=Kari A. O.|last7=Scott|first7=Anna M.|date=2021-11-24|title=The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis|url=https://pubmed.ncbi.nlm.nih.gov/34816481|journal=Neurourology and Urodynamics|volume=41 |issue=1 |pages=127–139 |doi=10.1002/nau.24839|issn=1520-6777|pmid=34816481|s2cid=244530010 ))</ref>

Some [[chemical weapons]] such as [[sarin]] or [[VX (nerve agent)|VX]], non-lethal [[riot control agent]]s such as [[CS gas|tear gas]], and insecticides such as [[diazinon]] fall into this category.

==Structure activity relationships for parasympathomimetic drugs<ref>((Cite web |url=http://pharmaxchange.info/notes/medicinal_chemistry/adrenergics_cholinergics.html |title=Medicinal Chemistry of Adrenergics and Cholinergics |access-date=2010-10-23 |archive-url=https://web.archive.org/web/20101104022742/http://pharmaxchange.info/notes/medicinal_chemistry/adrenergics_cholinergics.html |archive-date=2010-11-04 |url-status=dead ))</ref>==
For a cholinergic agent, the following criteria describe the structure activity relationship:
# Ing's Rule of 5: there should be no more than five atoms between the nitrogen and the terminal hydrogen for muscarinic (or cholinergic) activity;
# the molecule must possess a nitrogen atom capable of bearing a positive charge, preferably a quaternary ammonium salt;
# for maximum potency, the size of the alkyl groups substituted on the nitrogen should not exceed the size of a methyl group;
# the molecule should have an oxygen atom, preferably an ester-like oxygen capable of participating in a hydrogen bond;
# there should be a two-carbon unit between the oxygen atom and the nitrogen atom.

==Pharmaceuticals/Supplements==

===Direct-acting===
These act by stimulating the [[nicotinic acetylcholine receptor|nicotinic]] or [[muscarinic acetylcholine receptor|muscarinic]] receptors.
* '''Choline esters'''
** [[Acetylcholine]] (all [[acetylcholine receptors]])
** [[Bethanechol]] ([[M3 receptors]])
** [[Carbachol]] (all [[muscarinic receptors]] and some [[nicotinic receptors]])
** [[Methacholine]] (all [[muscarinic receptors]])
* '''Plant alkaloids'''
** [[Arecoline]]
** [[Nicotine]]
** [[Muscarine]]
** [[Pilocarpine]] ([[M3 receptors]])

===Indirect-acting===
Indirect acting parasympathomimetic substances may be either reversible cholinesterase inhibitors, irreversible cholinesterase inhibitors or substances that promote ACh release or [[anti-adrenergic]]s. The latter inhibits the antagonistic system, the [[sympathetic nervous system]].
* '''Reversible [[cholinesterase inhibitor]]s'''
** [[Donepezil]]
** [[Edrophonium]]
** [[Neostigmine]]
** [[Physostigmine]]
** [[Pyridostigmine]]
** [[Rivastigmine]]
** [[Tacrine]]
** [[Caffeine]] (non-competitive)<ref>((cite journal|pmid=2003276|year=1991|last1=Karadsheh|first1=N|last2=Kussie|first2=P|last3=Linthicum|first3=DS|title=Inhibition of acetylcholinesterase by caffeine, anabasine, methyl pyrrolidine and their derivatives|volume=55|issue=3|pages=335–42|journal=Toxicology Letters|doi=10.1016/0378-4274(91)90015-X))</ref>
** [[Huperzine A]]
* '''Irreversible cholinesterase inhibitors'''
** [[Echothiophate]]
** [[Isoflurophate]]
** [[Malathion]]
* '''ACh release promoters'''
** [[Alpha GPC]]
** [[Cisapride]]
** [[Droperidol]]
** [[Domperidone]]
** [[Metoclopramide]]
** [[Risperidone]]
** [[Paliperidone]]
* '''[[Anti-adrenergic]]s''': See also [[alpha blocker]] and [[beta blocker]]
** [[Clonidine]] ([[Alpha adrenergic receptor|α-receptor]] [[agonist]], [[Alpha-2 receptor|α<sub>2</sub>]] > [[alpha-1 receptor|α<sub>1</sub>]], giving [[negative feedback]])
** [[Methyldopa]] ([[Alpha-2 adrenergic receptor|α<sub>2</sub>]] agonist, giving [[negative feedback]])
** [[Propranolol]] ([[Beta adrenergic receptor|β-receptor]] [[antagonist]])
** [[Metoprolol]] ([[Beta adrenergic receptor|β-receptor]] [[antagonist]])
** [[Atenolol]] ([[Beta-1 adrenergic receptor|β<sub>1</sub>]] antagonist)
** [[Prazosin]] ([[Alpha-1 adrenergic receptor|α<sub>1</sub>]] antagonist)
** [[Oxymetazoline]] (partial α2 adrenergic agonist)

==See also==
* [[Sympathomimetic drug]]
* [[Parasympatholytics]]
* [[sympatholytics]]

== References ==
((reflist))

==External links==
* ((MeshName|Parasympathomimetics))

((Receptor agonists and antagonists))
((Cholinergics))
((Antiglaucoma preparations and miotics))

[[Category:Parasympathomimetics]]


((pharm-stub))

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