Muscarinic antagonist

Muscarinic-Acetylcholine receptor antagonist
Drug class

Scopolamine

Skeletal formula of Scopolamine, a nonselective antagonist of the muscarinic receptors
Class identifiers
Use Allergies, Asthma, Bradycardia, Motion sickness, Parkinson's disease, etc.
ATC code V
Biological target Metabotropic acetylcholinergic receptors.
External links
MeSH D018727
In Wikidata

A muscarinic receptor antagonist (MRA) is a type of anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor. Acetylcholine (often abbreviated ACh) is a neurotransmitter whose receptor is a protein found in synapses 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:

Most muscarinic receptor antagonists are synthetic chemicals; however, the two most commonly used anticholinergics, scopolamine and atropine, are belladonna alkaloids, and are naturally extracted.

Muscarinic antagonist effects and muscarinic agonist effects counterbalance each other for homeostasis.

Certain substances are known as long-acting muscarinic receptor antagonists (LAMAs).[1]

Effects

Scopolamine and atropine have similar effects on the peripheral nervous system. However, scopolamine has greater effects on the central nervous system (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. Scopolamine (Hyoscine) has anti-emetic activity and is, therefore, used to treat 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. In addition to increased activity to dopaminergic neurons from anticholinergics, antagonists of the muscarinic-acetylcholine receptors produce a sense of happiness and euphoria. This led to the discovery of various tricyclic antidepressants.

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 injection, 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 that 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[2] muscarinic antagonists include atropine, Hyoscyamine, hyoscine butylbromide and hydrobromide, ipratropium, tropicamide, cyclopentolate, and pirenzepine.

Muscarinic antagonists such as ipratropium bromide can also be effective in treating asthma, since acetylcholine is known to cause smooth muscle contraction, especially in the bronchi.

Comparison table

Substance Trade names Mechanism Clinical use Adverse effects
Atropine (D/L-Hyoscyamine) Symax, HyoMax, Anaspaz, Egazil, Buwecon, Cystospaz, Levsin, Levbid, Levsinex, Donnamar, NuLev, Spacol T/S and Neoquess non-selective antagonism, CNS depression[2]
Scopolamine (L-Hyoscine) Scopace, Transderm-Scop, Maldemar, Buscopan non-selective antagonism, CNS depression[2]
Hydroxyzine Vistaril, Atarax Very mild/negligible mechanism of action
Ipratropium Atrovent and Apovent non-selective antagonism, without any mucociliary excretion inhibition.[2] in asthma and bronchitis[2]
  • Bronchial vasodilation
Tropicamide short acting non-selective antagonism, CNS depression[2]
Pirenzepine M1 receptor-selective antagonist[2] (fewer than non-selective ones)[2]
Diphenhydramine Benadryl, Nytol Non-selective antagonism in the central nervous system, blood vessels and smooth muscle tissues
  • sedation
  • dry mouth
  • constipation
  • urinary retention
Doxylamine Unisom
  • antihistamine[4]
  • antiemetic
  • sleep aid
  • dizziness
  • dry mouth
Dimenhydrinate Dramamine Combination of diphenhydramine with a methylxanthine salt
Dicyclomine
Flavoxate Urispas
Oxybutynin Ditropan
Tiotropium Spiriva
Cyclopentolate short acting non-selective antagonism, CNS depression[2]
Atropine methonitrate non-selective antagonism, blocks transmission in ganglia.[2] Lacks CNS effects[5]
Trihexyphenidyl/Benzhexol Artane Targets the M1 Muscarinic receptor Parkinson's disease Drug at relative dose has 83% activity of atropine, thus has the same side-effects
Tolterodine Detrusitol, Detrol
Solifenacin Vesicare Competitive muscarinic acetylcholine receptor antagonist
Darifenacin Enablex Selective for M3 receptors [5] Urinary incontinence [5] Few side effects[5]
Benztropine 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, in particular of the colon.
  • Irritable bowel syndrome in its primary form (e.g., Abdominal Pain, Bloating, Constipation, and Diarrhea).
  • Irritable bowel syndrome associated with organic lesions of the gastrointestinal tract. (e.g., diverticulosis & diverticulitis, etc.).
  • skin rashes
Procyclidine Antimuscarinic
  • Drug-induced parkinsonism, akathisia and acute dystonia
  • Parkinson disease
  • Idiopathic or secondary dystonia
 Overdose produces confusion, agitation and sleeplessness that can last up to or more than 24 hours. Pupils become dilated and unreactive to light. Tachycardia (fast heart beat), as well as auditory and visual hallucinations
Aclidinium bromide Tudorza Selective long acting muscarinic antagonist
  • Bronchospasm
  • Chronic Obstructive Pulmonary Disease

See also

References

  1. ↑ Alagha, Khudar; et al. (March 2014). "Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases". Therapeutic Advances in Chrnoic Disease. 5 (2): 85–98. PMC 3926345 Freely accessible. PMID 24587893. doi:10.1177/2040622313518227. Three long-acting muscarinic receptor antagonists (LAMAs) were approved ...
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 147
  3. ↑ Mirakhur, RK (August 1991). "Preanaesthetic medication: a survey of current usage". Journal of the Royal Society of Medicine. 84 (8): 481–483. PMC 1293378 Freely accessible. PMID 1886116.
  4. ↑ http://www.drugbank.ca/drugs/DB00366
  5. 1 2 3 4 Table 10-5 in: Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007). Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-06911-5.
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