Muscarinic antagonist Information & Muscarinic antagonist Links at HealthHaven.com

In neurochemistry, a muscarinic receptor antagonist is an agent that reduces the activity of the muscarinic acetylcholine receptor. Acetylcholine (often abbreviated ACh) is a neurotransmitter, whose receptor is a protein found in synapse and other cell membranes. Besides responding to their primary neurochemical, neurotransmitter receptors can be sensitive to a variety of other molecules. Acetylcholine receptors are classified into two groups based on this - muscarinic, which also respond to muscarine, and nicotinic which respond to nicotine.

Most muscarinic receptor antagonists are synthetic, but scopolamine and atropine are belladonna alkaloids, and are naturally extracted.

[edit] Effects

[edit] Effect on central nervous system

Scopolamine and atropine have similar effects on the peripherial nervous system, however, scopolamine has greater effects on the CNS than atropine due to its ability to cross the blood-brain barrier. At higher than therapeutic doses, atropine and scopolamine cause CNS depression characterized by amnesia, fatigue and reduction in rapid eye movement sleep. Hyoscine has anti-emetic activity, so is used for 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 (nigrostriatal 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.

[edit] Effect on heart

Atropine acts on the M2 receptors of the heart and antagonizes the activity of acetylcholine. It causes tachycardia by blocking vagal effects on the sinoatrial node. Acetylcholine hyperpolarizes the sinoatrial 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 (autoreceptors). Intake of acetylcholine in axoplasm is prevented and the presynaptic nerve releases more acetylcholine into the synapse which initially causes bradycardia.

In the atrioventricular node, the resting potential is abbreviated which facilitates conduction. This is seen as a shortened PR-interval on an electrocardiogram.

It has an opposite effect on blood pressure. Tachycardia and stimulation of the vasomotor center causes an increase in blood pressure. But due to feed back regulation of the vasomotor center, there is fall in blood pressure due to vasodilation.

Important^[1] muscarinic antagonists include atropine, hyoscine, ipratropium, tropicamide, cyclopentolate and pirenzepine.

[edit] Comparison table

Substance	Trade names	Mechanism^[2]	Clinical use^[2]	Adverse effects^[2]
Atropine (D/L-Hyoscyamine)		non-selective antagonism, CNS depression	in anaesthesia^[3] 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	Atrovent and Apovent	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	Ditropan		overactive bladder urge incontinence
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		Parkinson's disease
Tolterodine	Detrusitol, Detrol
Solifenacin	Vesicare	Competitive muscarinic acetylcholine receptor antagonist	overactive bladder (OAB) Urgency (urge incontinence)
Darifenacin	Enablex
Benzatropine	Cogentin	Reduces the effects of the relative central cholinergic excess that occurs as a result of dopamine deficiency.	Parkinson's disease
Mebeverine	Colofac, Duspatal, Duspatalin	A muscolotropic spasmolytic with a strong and selective action on the smooth muscle spasm of the gastrointestinal tract, particularly of the colon.	Irritable bowel syndrome in its primary form (eg. Abdominal Pain, Bloating, Constipation, and Diarrhea). Irritable bowel syndrome associated with organic lesions of the gastrointestinal tract. (eg. diverticulosis & diverticulitis, etc.).	skin rashes

[edit] See also

[edit] References

^ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 147
^ ^a ^b ^c Unless else specified in table boxes, then ref is: Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 147
^ Mirakhur, RK (August 1991). "Preanaesthetic medication: a survey of current usage". Journal of the Royal Society of Medicine 84 (8): 481–483. PMID 1886116. http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1293378&blobtype=pdf.

[edit] External links

[Rang147-0] Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 147

[Rang147Unless-1] Unless else specified in table boxes, then ref is: Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 147

[Mirakhur-2] Mirakhur, RK (August 1991). "Preanaesthetic medication: a survey of current usage". Journal of the Royal Society of Medicine 84 (8): 481–483. PMID 1886116. http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1293378&blobtype=pdf.

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