Parasympathomimetic drug
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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:
- 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 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
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
- ACh release promoters
- 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
References
- ^ a b 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.
- ^ a b 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.
- ^ "Dorlands Medical Dictionary:parasympathomimetic". Archived from the original on 2009-07-26.
- ^ Parasympathomimetics
- ^ Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6
- ^ 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.
- ^ "Medicinal Chemistry of Adrenergics and Cholinergics". Archived from the original on 2010-11-04. Retrieved 2010-10-23.
- ^ 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)