Parasympathomimetic drug

This article is about drugs stimulating parasympathetic system. For drugs inhibiting parasympathetic system, see parasympatholytics.

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

For a cholinergic agent, the following criteria describe the structure activity relationship:^[7]

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
• Sympatholytics