Definition of Cholinergic Blocking Agents (Cholinolytics / Anticholinergics)
- Cholinergic Blocking Agents (Cholinolytics / Anticholinergics) are compounds that inhibit the actions of acetylcholine (ACh) at muscarinic receptors (primarily), and in some cases, nicotinic receptors.
- They are also known as antimuscarinic agents or muscarinic antagonists.
- They block parasympathetic nerve impulses, leading to sympathomimetic effects, such as decreased gland secretion, relaxation of smooth muscles, pupil dilation, and increased heart rate.
Structure–Activity Relationship (SAR) of Cholinolytic Agents
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Basic Nitrogen:
- Typically, a tertiary amine (e.g., atropine) or quaternary ammonium (e.g., ipratropium).
- Tertiary amines cross the blood-brain barrier (CNS effects); quaternary compounds are peripherally acting.
-
Alkyl Substituents on Nitrogen:
- Small groups (e.g., methyl, isopropyl) enhance antagonistic potency.
- Bulky groups reduce agonist activity, promoting antagonism.
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Ester Group:
- Common in classical structures; can be replaced by ethers or alcohols in synthetic analogs.
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Hydrophobic/Aromatic Moiety:
- Attached to the acyl region (e.g., phenyl, cycloalkyl, heterocycles).
- Enhances binding to the receptor’s hydrophobic pocket.
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Nitrogen–Oxygen Distance:
- Optimal spacing of 2–4 carbon atoms improves receptor binding.
-
Acyl Substituents:
- Bulky groups increase receptor selectivity and antagonistic activity.
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Classification of Cholinergic Blocking Agents
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Solanaceous Alkaloids and Analogues (Naturally occurring or derived)
- These are either derived from or structurally similar to tropane alkaloids found in plants like Atropa belladonna and Datura stramonium.
-
Synthetic Cholinergic Blocking Agents
- These agents are structurally diverse and designed to enhance selectivity, reduce side effects, or limit CNS activity.
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