|Muscarinic-Acetylcholine receptor antagonist|
|Use||Allergies, Asthma, Bradycardia, Motion sickness, Parkinson's disease, etc.|
|Biological target||Metabotropic acetylcholinergic receptors.|
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:
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.
|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|
|Scopolamine (L-Hyoscine)||Scopace, Transderm-Scop, Maldemar, Buscopan||non-selective antagonism, CNS depression||
|Hydroxyzine||Vistaril, Atarax||Very mild/negligible mechanism of action|
|Ipratropium||Atrovent and Apovent||non-selective antagonism, without any mucociliary excretion inhibition.||in asthma and bronchitis||
|Tropicamide||short acting non-selective antagonism, CNS depression||
|Pirenzepine|| M1 receptor-selective antagonist
||(fewer than non-selective ones)|
|Diphenhydramine||Benadryl, Nytol||Non-selective antagonism in the central nervous system, blood vessels and smooth muscle tissues||
|Dimenhydrinate||Dramamine||Combination of diphenhydramine with a methylxanthine salt|
|Cyclopentolate||short acting non-selective antagonism, CNS depression||
|Atropine methonitrate||non-selective antagonism, blocks transmission in ganglia. Lacks CNS effects||
|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|
|Solifenacin||Vesicare||Competitive muscarinic acetylcholine receptor antagonist|
|Darifenacin||Enablex||Selective for M3 receptors||Urinary incontinence||Few side effects|
|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, in particular of the colon.||
||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||
- 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. doi:10.1177/2040622313518227. PMC 3926345.
Three long-acting muscarinic receptor antagonists (LAMAs) were approved ...
- 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. PMC 1293378. PMID 1886116.
- 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.
- Effects of Muscarinic Antagonist
- Atropine (Muscarinic Receptor Antagonist), Cardiovascular Pharmacology Concepts, Richard E. Klabunde, PhD
- Muscarinic antagonists at the US National Library of Medicine Medical Subject Headings (MeSH)
- MeSH list of agents 82018727