15. Muscarinic receptor antagonists

Last updated on January 10, 2019 at 19:32

Muscarinic receptor antagonists
Non-selective M1-selective
Tertiary ammonium compounds Quaternary ammonium compounds
Atropine Ipratropium Pirenzepine
Cyclopentolate
Homatropine
Scopolamine
Tropicamide

This class of drugs are competitive antagonists of muscarinic receptors, so they decrease parasympathetic activation. Because of this are they called parasympatholytics or cholinolytics. They are mostly non-selective (meaning they act on all muscarinic receptor subtypes, not just one subtype), but a few are selective.

All of them contain a tertiary ammonium group except for ipratropium. Because the quaternary ammonium group has a positive charge will drugs with this group will be less lipophilic and therefore unable to cross the blood-brain barrier to have any effects on the CNS. Drugs with the tertiary ammonium group can cross the BBB and will have CNS effects. Tertiary ammonium drugs are also much better absorbed through the GI tract than quaternary drugs. This goes for all drugs, not just for parasympatholytics.

They have the following effects (mostly the opposite of the parasympathetic system):

  • Mydriasis, increased intraocular pressure, cycloplegia (they block accommodation), decreased tear secretion, photophobia
  • Tachycardia
  • Bronchodilation, decreased bronchial secretion
  • Decreased gastrointestinal secretion, decreased motility and peristalsis, relaxation of sphincters
  • Relaxation of detrusor muscle
  • Decreased sweating, hyperthermia in high doses (due to the decreased sweating)

Atropine comes from a plant called atropa belladonna, so it’s a natural, tertiary amine alkaloid. In low doses it acts as a stimulant on the CNS, but in high doses it leads to hallucination and disorientation. Atropine is used to:

  • decrease bronchial secretions and dilate the bronchi during anaesthesia.
  • treat bronchospasm
  • treat sinus bradycardia, slow AV conduction and carotid sinus hyperesthesia
  • treat iritis and iridocyclitis.
  • treat hypersecretion of saliva
  • treat intestinal hypermotility
  • treat muscarine and organic phosphate poisoning

The symptoms of atropine intoxication are:

  • Tachycardia
  • Hot, dry, red skin
  • Hyperthermia
  • Confusion, hallucination, convolution

Atropine intoxication is treated with physostigmine, diazepam and cooling.

Atropine is used as pre-treatment for surgeries, to decrease saliva and bronchial secretion. When muscarinic receptors are blocked by atropine will the effect of acetylcholine on nicotinic receptors be increased. This can cause a pressor effect (blood pressure elevation) because nicotinic receptors on sympathetic ganglia and adrenal medulla are activated more than normal. This effect can be counteracted with ganglionic blockers or sympatholytics.

Scopolamine is also a tertiary amine alkaloid found in atropa belladonna. It is a sedative and causes amnesia in low doses but is stimulatory in high doses. It’s used to treat motion sickness by acting on the vestibular system. Scopolamine can be absorbed through the skin. It can also be used as eyedrops. It can also treat Parkinson’s.

Ipratropium is a synthetic quaternary compound, used to treat asthma and bronchitis by inhalation.

Tropicamide and cyclopentolate are tertiary ammonium compounds used as eyedrops to induce mydriasis and cycloplegia (paralysis of the ciliary muscle) for examination of the eye. They are short-acting. Homatropine does the same, but has intermediate duration of action.

Pirenzepine is unique in that it is a selective muscarinic subtype 1 (M1) antagonist. It inhibits gastric secretions and is used against peptic ulcers and has few side-effects.

Generally speaking are the parietal cells and CNS innervated by M1, heart innervated by M2, while M3 innervates the rest, e.g. the eye, GI tract, bronchial smooth muscle and salivary gland secretion.

Centrally-acting muscarinic antagonists like scopolamine can be used to treat Parkinson’s, however they have so many peripheral side effects, so they’re not widely used. In Norway is a drug called biperiden, a centrally acting M1 inhibitor (not to be known for the exam) used instead, as it has fewer peripheral effects than atropine.


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14. Cholinergic agonists and cholinesterase inhibitors

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16. Neuromuscular blocking agents

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