Muscarinic antagonist


Muscarinic antagonist

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 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, but scopolamine and atropine are belladonna alkaloids, and are naturally extracted.

Contents

Effects

Scopolamine and atropine have similar effects on the peripheral 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.

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 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 Clinical use Adverse effects
Atropine (D/L-Hyoscyamine) non-selective antagonism, CNS stimulation[1]
Scopolamine (L-Hyoscine) Scopace, Transderm-Scop, Maldemar, Buscopan non-selective antagonism, CNS depression[1]
Ipratropium Atrovent and Apovent non-selective antagonism, without any mucociliary excretion inhibition.[1]
Tropicamide short acting non-selective antagonism, CNS depression[1]
Pirenzepine M1 receptor-selective antagonist[1]
  • inhibits gastric secretion[1]
(fewer than non-selective ones)[1]
Diphenhydramine Benadryl
  • for extrapyramidal symptoms from typical antipsychotic medications
  • antihistamine
  • sleep aid
Dimenhydrinate Dramamine
Dicyclomine
Flavoxate
Oxybutynin Ditropan
Tiotropium Spiriva
Cyclopentolate short acting non-selective antagonism, CNS depression[1]
Atropine methonitrate non-selective antagonism, blocks transmission in ganglia.[1] Lacks CNS effects[3]
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 [3] Urinary incontinence [3] Few side effects[3]
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 (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; and
  • 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

See also

References

  1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4.  Page 147
  2. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1293378. 
  3. ^ a b c d 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. 

External links