Parasympathomimetic drug explained

A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS).^{[1] [2]} These chemicals are also called cholinergic drugs because acetylcholine (ACh) is the neurotransmitter used by the PSNS.^{[3] [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

Notes and References

1. Web site: Dorlands Medical Dictionary:parasympathomimetic . 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 . 2009-07-26 . dead .
2. Book: Forrester . John V. . Dick . Andrew D. . McMenamin . Paul G. . Roberts . Fiona . Pearlman . Eric . The Eye . General and ocular pharmacology . Elsevier . 2016 . 978-0-7020-5554-6 . 10.1016/b978-0-7020-5554-6.00006-x . 338–369.e1 . 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. Book: Dowd, Frank . Pharmacology and therapeutics for dentistry: Chapter 6 - Cholinergic Agonists and Muscarinic Receptor Antagonists . Elsevier . St. Louis, Missouri . 2017 . 978-0-323-39307-2 . 958121223 . 82–97 .
4. https://www.ncbi.nlm.nih.gov/mesh/68010277 Parasympathomimetics
5. Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company.
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 . 10.1002/nau.24839. 1520-6777. 34816481. 244530010 .
7. Web site: Medicinal Chemistry of Adrenergics and Cholinergics . 2010-10-23 . https://web.archive.org/web/20101104022742/http://pharmaxchange.info/notes/medicinal_chemistry/adrenergics_cholinergics.html . 2010-11-04 . dead .
8. 2003276. 1991. Karadsheh. N. Kussie. P. Linthicum. DS. Inhibition of acetylcholinesterase by caffeine, anabasine, methyl pyrrolidine and their derivatives. 55. 3. 335–42. Toxicology Letters. 10.1016/0378-4274(91)90015-X.