Study Notes: Nicotinic vs. Muscarinic Receptors

1. Autonomic Nervous System Overview

• Sympathetic (thoracolumbar) = “Fight or flight.”

• Parasympathetic (craniosacral) = “Rest and digest.”

• Pathway: Preganglionic fiber → Ganglion → Postganglionic fiber.

  • Preganglionic = cholinergic (releases acetylcholine).

  • Receptors at ganglion = Nicotinic N (Nn).

  • Postganglionic:

    • Parasympathetic = ACh → Muscarinic receptors.

    • Sympathetic = Norepinephrine → Adrenergic receptors (except sweat glands → ACh → Muscarinic).

• Adrenal medulla = Modified ganglion; receptor is Nn → directly secretes epinephrine/norepinephrine into blood.

2. Somatic Nervous System

• Upper motor neuron (brain) → Lower motor neuron (anterior horn cell) → Skeletal muscle.

• Receptors at neuromuscular junction = Nicotinic M (Nm).

• Function: voluntary skeletal muscle contraction.

3. Nicotinic Receptors

• Subtypes:

  • Nn = Neurons (autonomic ganglia, adrenal medulla).

  • Nm = Muscle (skeletal muscle at neuromuscular junction).

• Mechanism:

  • Ion channel → ↑ Na⁺ influx → Depolarization → Activation.

• Dose-dependent effect:

  • Low dose nicotine = Stimulation.

  • High dose nicotine (or succinylcholine) = Desensitization/inhibition → paralysis.

4. Muscarinic Receptors

• Found in smooth muscle, cardiac muscle, glands, and peripheral tissues.

• Subtypes:

  • M1, M3, M5 = Gq (excitatory) → ↑ Ca²⁺ → contraction/secretion.

  • M2, M4 = Gi (inhibitory) → ↓ cAMP → inhibition.

• Distribution & Actions:

  • M1: Brain (↑ cognitive function, gastric secretion).

  • M2: Heart (↓ HR, ↓ contractility).

  • M3: Glands (↑ secretions: tears, saliva, gastric, bronchial), Smooth muscle (contraction in GI, bladder, bronchi), Eye (pupil constriction, accommodation), Blood vessels (vasodilation via NO).

  • M4, M5: Mainly CNS.

5. Functional Summary

• Parasympathetic effects (via muscarinic):

  • Heart: M2 → ↓ HR, ↓ contractility.

  • Lungs: M3 → bronchoconstriction, ↑ secretions.

  • GI/GU: M3 → ↑ motility, ↑ secretions, bladder contraction.

  • Eye: M3 → miosis (pupil constriction), accommodation.

  • Glands: M1 & M3 → ↑ secretions (tears, saliva, sweat).

  • Vessels: M3 (via NO) → vasodilation.

6. Pharmacology

• Muscarinic Agonists:

  • Direct: Acetylcholine, Methacholine, Carbachol, Bethanechol, Pilocarpine, Cevimeline.

  • Indirect (AChE inhibitors): Neostigmine, Pyridostigmine, Rivastigmine, Physostigmine, Donepezil.

• Muscarinic Antagonists:

  • Atropine, Ipratropium, Tiotropium, Benztropine, Tropicamide.

• Nn Blockers (Ganglion blockers):

  • Hexamethonium, Mecamylamine.

• Nm Agonist:

  • Succinylcholine (depolarizing blocker: Phase 1 = fasciculations, Phase 2 = paralysis).

• Nm Antagonists (Non-depolarizing blockers):

  • Drugs ending in “-curium” or “-curonium” (e.g., Tubocurarine, Atracurium, Pancuronium, Vecuronium, Rocuronium).

  • Used in anesthesia for muscle paralysis.

7. Clinical Pearls

• Succinylcholine: Must check cholinesterase levels before use (risk of prolonged paralysis/apnea).

• Asthma patients: Parasympathetic activation (M3) causes bronchoconstriction → muscarinic antagonists (ipratropium/tiotropium) relieve symptoms.

• Blood vessels: Parasympathetic vasodilation occurs indirectly via M3-mediated nitric oxide.

• Sympathetic exception: Sweat glands are sympathetic but cholinergic (ACh → M3).

Quick Mnemonics

• Nn = Neurons (ganglia, adrenal medulla).

• Nm = Muscles (skeletal NMJ).

• M1, M3, M5 = Gq → contraction/secretion.

• M2, M4 = Gi → inhibition.