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.
Effects
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.
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.
Comparison table
| Substance |
Trade names |
Mechanism[2] |
Clinical use[2] |
Adverse effects[2] |
| Atropine (D/L-Hyoscyamine) |
|
non-selective antagonism, CNS depression |
|
|
| Scopolamine (L-Hyoscine) |
|
non-selective antagonism, CNS depression |
|
|
| Ipratropium |
Atrovent and Apovent |
non-selective antagonism, without any mucociliary excretion inhibition. |
|
|
| Tropicamide |
|
short acting non-selective antagonism, CNS depression |
|
|
| Pirenzepine |
|
M1 receptor-selective antagonist
|
|
(fewer than non-selective ones) |
| Diphenhydramine |
Benadryl |
|
|
|
| Dimenhydrinate |
Dramamine |
|
|
|
| Dicyclomine |
|
|
|
|
| Flavoxate |
|
|
|
|
| Oxybutynin |
Ditropan |
|
|
|
| Tiotropium |
Spiriva |
|
|
|
| Cyclopentolate |
|
short acting non-selective antagonism, CNS depression |
|
|
| Atropine methonitrate |
|
non-selective antagonism, blocks transmission in ganglia |
|
|
| Trihexyphenidyl |
Artane |
|
Parkinson's disease |
|
| Tolterodine |
Detrusitol, Detrol |
|
|
|
| Solifenacin |
Vesicare |
Competitive muscarinic acetylcholine receptor antagonist |
|
|
| 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.).
|
|
See also
References
External links
