Muscarinic antagonist

A muscarinic receptor antagonist is an agent that reduces the activity of the muscarinic acetylcholine receptor. Most of them are synthetic, but scopolamine and atropine are belladonna alkaloids, and are naturally extracted.

Effects

Effect on CNS

Muscarinic antagonists stimulate the CNS as a result of stimulation of medulla and higher cerebral centers. At low doses of atropine, it causes slight restlessness; at high or toxic doses it causes restlessness, agitation, and hallucinations. In atropine poisoning, marked excitation and agitation leads to hyperactivity and increase in body temperature through inhibition of sweating. Scopolamine in therapeutic doses causes CNS depression characterized by amnesia, fatigue and reduction in REM (Rapid Eye Movement) sleep. Hyoscine has anti-emetic activity, so is used in motion sickness.

Antimuscarinics are also used as anti-parkinsonian drugs. In Parkinsonism, there is imbalance between levels of acetylcholine and dopamine in the brain, involving both increased levels of acetylcholine and degeneration of dopaminergic pathways (nigro-striatal pathway). Thus, in Parkinsonism there is decreased level of dopaminergic activity. One method of balancing the neurotransmitters is through blocking central cholinergic activity using muscarinic receptor antagonists.

Effect on heart

Atropine acts on the M2-receptors of the heart and antagonizes the activity of Ach. It causes tachycardia by blocking vagal effects on the SA node. Ach hyperpolarizes the SA node which is overcome by MRA and thus increases the heart rate. If atropine is given by intramuscular or subcutaneous, it causes initial bradycardia. This is because by i.m/s.c it acts on presynaptic M1-receptors (auto receptors). Intake of Ach in axoplasm is prevented and the presynaptic nerve releases more Ach into the synapse which initially causes bradycardia.

In the AV node, the resting potential (RP) is abbreviated which facilitates conduction. This is seen as a shortened PR-interval on EKG.

It has an opposite effect on Blood Pressure. Tachycardia and stimulation of the vasomotor center causes an increase in BP. But due to feed back regulation of VMC there is fall in BP due to vasodilation.

Important muscarinic antagonists include atropine, hyoscine, ipratropium, tropicamide, cyclopentolate and pirenzepine...

Comparison table

Substance	Trade names	Mechanism	Clinical use	Adverse effects
Atropine (D/L-Hyoscyamine)		non-selective antagonism, CNS stimulation	in anaesthesia anticholinesterase poisoning bradycardia antispasmodic in gastrointestinal hypermotility	urinary retention xerostomia blurred vision
Scopolamine (L-Hyoscine)		non-selective antagonism, CNS depression	as atropine motion sickness	as atropine sedation
Ipratropium		non-selective antagonism, without any mucociliary excretion inhibition.	in asthma and bronchitis
Tropicamide		short acting non-selective antagonism, CNS depression	produce mydriasis and cycloplegia in diagnostics	may cause ocular hypertension
Pirenzepine		M1 receptor-selective antagonist inhibits gastric secretion	in peptic ulcer (not much anymore)	(fewer than non-selective ones)
Diphenhydramine	Benadryl		for extrapyramidal symptoms from typical antipsychotic medications
Dimenhydrinate	Dramamine		motion sickness
Dicyclomine
Flavoxate
Oxybutynin
Tiotropium	Spiriva		Chronic obstructive pulmonary disease
Cyclopentolate		short acting non-selective antagonism, CNS depression	produce mydriasis and cycloplegia in diagnostics	may cause ocular hypertension
Atropine methonitrate		non-selective antagonism, blocks transmission in ganglia	antispasmodic in gastrointestinal hypermotility	* *
Trihexyphenidyl	Artane
Tolterodine	Detrusitol
Solifenacin	Vesicare
Darifenacin	Enablex
Benzatropine	Cogentin	Reduces the effects of the relative central cholinergic excess that occurs as a result of dopamine deficiency.	Anti-Parkinsonian Drug
Mebeverine	Colofac

See also

Muscarinic agonist

Parasympatholytic

Anticholinergic

References

External links

• Effects of Muscarinic Antagonist
• http://cvpharmacology.com/antiarrhy/atropine.htm