Medical Pharmacology: Cholinergic Pharmacology

Medical Pharmacology Chapter 6: Autonomic Pharmacology: Cholinergic Drugs

Cholinergic Receptors: Subtypes, Tissues, Responses and Molecular Mechanisms

Muscarinic Receptor Coupling Mechanisms

**"Muscarinic Cholinergic Receptors"**

Attribution: The Noted Anatomist Muscarinic Cholinergic Receptors 2/20/2021 https://www.youtube.com/watch?v=5sB_ZcK1kgY https://www.youtube.com/channel/UCe9lb3da4XAnN7v3ciTyquQ (The Noted Anatomist YouTube Site)

Five types of cholinergic receptors have been identified by molecular cloning methods.
The five muscarinic receptor subtypes, M₁ - M_5, are associated with specific anatomical sites. For example:
- M₁ -ganglia; secretory glands
- M₂ - myocardium, smooth muscle
- M₃ , M₄ :smooth muscle, secretory glands

**Nicotinic Muscle Receptor**
Antagonists	Tissue	Responses	Molecular Aspects
Tubocurarine α-bungarotoxin	Neuromuscular Junction	Membrane Depolarization leading to muscle contraction	Nicotinic (muscle) receptor's ion channel opening

**Nicotinic Neuronal Receptor**
Antagonists	Tissue	Responses	Molecular Aspects
Mecamylamine (Inversine)	Autonomic Ganglia	Depolarization: postsynaptic cell activation	Nicotinic (muscle) receptor's ion channel opening
	Adrenal Medulla	Catecholamine secretion
	CNS	unknown

**Muscarinic Type M₁**
Antagonist	Tissue	Responses	Molecular Aspects
Atropine Pirenzepine (more selective)	Autonomic Ganglia	Depolarization (late EPSP)	Stimulation of Phospholipase C leading to increased cytosolic Ca²⁺ .
Atropine Pirenzepine (more selective)	CNS	Unknown

**Muscarinic Type M₂**
Tissue (Heart)	Responses	Molecular Aspects
SA node	Decreased phase 4 depolarization; hyperpolarization	K⁺channel activation through ß-γ G_i subunits; G_i -mediated inhibition of adenylyl cyclase which decreases intracellular Ca²⁺ levels. G_i can inhibit directly Ca²⁺ channel opening.
Atrium	Decreased contractility; decreased AP duration
AV node	Decreased conduction velocity
Ventricle	Decreased contractility

Adapted from Table 6-2: Lefkowitz, R.J, Hoffman, B.B and Taylor, P. Neurotransmission: The Autonomic and Somatic Motor Nervous Systems, In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, p119.

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