Cholinergic blocking agents, also known as anticholinergic drugs, are a type of medication that inhibits the action of acetylcholine, a neurotransmitter, in the central and the peripheral nervous system.
They work by blocking the muscarinic acetylcholine receptors, which are found in various parts of the body including the brain, heart, smooth muscles, and glands.
There are two primary types of cholinergic blocking agents:
1.Muscarinic Antagonists (also known as antimuscarinic agents):
These drugs block the action of acetylcholine at muscarinic receptors.
Examples include atropine, scopolamine, and ipratropium.
They are used to treat a variety of conditions such as gastrointestinal disorders, urinary incontinence, COPD, and certain types of poisoning.
2.Ganglionic Blockers:
These drugs block the action of acetylcholine at nicotinic receptors found in autonomic ganglia.
Examples include mecamylamine and hexamethonium.
They are not commonly used due to their significant side effects but have historically been used in the treatment of hypertension.
In addition to these, some drugs block the action of acetylcholine at the level of the neuromuscular junction. These are known as neuromuscular blockers and are used mainly in anesthesia to produce muscle relaxation.
SAR of cholinolytic agents:
The Structure-Activity Relationship (SAR) of cholinolytic (anticholinergic) agents can be summarized as follows:
A tertiary amine structure is needed for CNS activity. Quaternary amines, on the other hand, do not penetrate the CNS and act peripherally.
The presence of an ester group or a carbonyl group adjacent to the nitrogen increases the antimuscarinic activity.
Increasing the length of the hydrocarbon chain connecting the amine and the aromatic ring generally increases activity up to three carbon atoms. Beyond this, activity decreases.
Substitution on the aromatic ring with non-polar groups enhances activity.
Classification of Cholinergic Blocking agents:
Solanaceous alkaloids and analogues:
Solanaceous alkaloids are a group of naturally occurring compounds found in plants belonging to the Solanaceae family, which includes species such as deadly nightshade (Atropa belladonna), henbane (Hyoscyamus niger), mandrake (Mandragora officinarum), and datura (Datura spp.). These alkaloids primarily act as cholinergic antagonists by blocking muscarinic acetylcholine receptors, leading to anticholinergic effects.