Parasympathomimetic drug

A parasympathomimetic drug is a drug or poison that acts by stimulating or mimicking the parasympathetic nervous system (PSNS).^[1] These chemicals are also called cholinergic drugs because acetylcholine (ACh) is the neurotransmitter used by the PSNS. Chemicals in this family can act either directly by stimulating the nicotinic or muscarinic receptors, or indirectly by inhibiting cholinesterase, promoting acetylcholine release, or other mechanisms. ^[2]

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^[3]

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. 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

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 drugs may be either reversible cholinesterase inhibitors, irreversible cholinesterase inhibitors or drugs 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
• Irreversible cholinesterase inhibitors
  • Echothiophate
  • Isoflurophate
  • Malathion
• ACh release promoters
  • Cisapride
  • Metoclopramide
• Anti-adrenergics
  • clonidine (α-receptor agonist, α₂ > α₁, giving negative feedback)
  • methyldopa (α₂ agonist, giving negative feedback)
  • propranolol (β-receptor antagonist)
  • atenolol (β₁ antagonist)
  • prazosin (α₁ antagonist)

See also

• Sympathomimetic drug

Notes

1. ^ "Dorlands Medical Dictionary:parasympathomimetic". http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp?pg=/ppdocs/us/common/dorlands/dorland/six/000078652.htm. 
2. ^ Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6
3. ^ Medicinal Chemistry of Adrenergics and Cholinergics

External links

• MeSH Parasympathomimetics