Parasympathomimetic drug

A parasympathomimetic drug, sometimes called a cholinomimetic drug^[1] or cholinergic receptor stimulating agent,^[2] is a substance that stimulates the parasympathetic nervous system (PSNS).^[3][2] These chemicals are also called cholinergic drugs because acetylcholine (ACh) is the neurotransmitter used by the PSNS.^[1][4] Chemicals in this family can act either directly by stimulating the nicotinic or muscarinic receptors (thus mimicking acetylcholine), or indirectly by inhibiting cholinesterase, promoting acetylcholine release, or other mechanisms.^[5] Common uses of parasympathomimetics include glaucoma, Sjögren syndrome and underactive bladder.^[6]

Some chemical weapons such as sarin or VX, non-lethal riot control agents such as tear gas, and insecticides such as diazinon fall into this category.

Structure activity relationships for parasympathomimetic drugs[7]

For a cholinergic agent, the following criteria describe the structure activity relationship:

1. 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;
2. the molecule must possess a nitrogen atom capable of bearing a positive charge, preferably a quaternary ammonium salt;
3. for maximum potency, the size of the alkyl groups substituted on the nitrogen should not exceed the size of a methyl group;
4. the molecule should have an oxygen atom, preferably an ester-like oxygen capable of participating in a hydrogen bond;
5. 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 or 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-adrenergics. The latter inhibits the antagonistic system, the sympathetic nervous system.

• Reversible cholinesterase inhibitors
  • Donepezil
  • Edrophonium
  • Neostigmine
  • Physostigmine
  • Pyridostigmine
  • Rivastigmine
  • Tacrine
  • Caffeine (non-competitive)^[8]
  • Huperzine A
• Irreversible cholinesterase inhibitors
  • Echothiophate
  • Isoflurophate
  • Malathion
• ACh release promoters
  • Alpha GPC
  • Cisapride
  • Droperidol
  • Domperidone
  • Metoclopramide
  • Risperidone
  • Paliperidone
• Anti-adrenergics: See also alpha blocker and beta blocker
  • Clonidine (α-receptor agonist, α₂ > α₁, giving negative feedback)
  • Methyldopa (α₂ agonist, giving negative feedback)
  • Propranolol (β-receptor antagonist)
  • Metoprolol (β-receptor antagonist)
  • Atenolol (β₁ antagonist)
  • Prazosin (α₁ antagonist)
  • Oxymetazoline (partial α2 adrenergic agonist)

See also

• Sympathomimetic drug
• Parasympatholytics
• Sympatholytics

References

1. Dowd, Frank (2017). Pharmacology and therapeutics for dentistry: Chapter 6 - Cholinergic Agonists and Muscarinic Receptor Antagonists. St. Louis, Missouri: Elsevier. pp. 82–97. ISBN 978-0-323-39307-2. OCLC 958121223.
2. Forrester, John V.; Dick, Andrew D.; McMenamin, Paul G.; Roberts, Fiona; Pearlman, Eric (2016). "General and ocular pharmacology". The Eye. Elsevier. pp. 338–369.e1. doi:10.1016/b978-0-7020-5554-6.00006-x. ISBN 978-0-7020-5554-6. 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.
3. "Dorlands Medical Dictionary:parasympathomimetic". Archived from the original on 2009-07-26.
4. Parasympathomimetics
5. Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6
6. Moro, Christian; Phelps, Charlotte; Veer, Vineesha; Clark, Justin; Glasziou, Paul; Tikkinen, Kari A. O.; Scott, Anna M. (2021-11-24). "The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis". Neurourology and Urodynamics. 41 (1): 127–139. doi:10.1002/nau.24839. ISSN 1520-6777. PMID 34816481. S2CID 244530010.
7. "Medicinal Chemistry of Adrenergics and Cholinergics". Archived from the original on 2010-11-04. Retrieved 2010-10-23.
8. Karadsheh, N; Kussie, P; Linthicum, DS (1991). "Inhibition of acetylcholinesterase by caffeine, anabasine, methyl pyrrolidine and their derivatives". Toxicology Letters. 55 (3): 335–42. doi:10.1016/0378-4274(91)90015-X. PMID 2003276.

External links

• Parasympathomimetics at the U.S. National Library of Medicine Medical Subject Headings (MeSH)