[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › Cholinergic transmission [Pharmacology](https://durgical.com/en/pharmacology/) · Topic # Cholinergic transmission How nerve cells make, release and break down acetylcholine, the two receptor families it acts on, and the drugs and poisons that target each step. Updated 2026-11-01 Acetylcholine is the transmitter of all autonomic ganglia, the parasympathetic nerve endings, sympathetic fibres to sweat glands, the neuromuscular junction and many brain pathways. Its life cycle (synthesis, storage, release, receptor action and breakdown by acetylcholinesterase) offers several drug targets, from anaesthesia and myasthenia gravis to glaucoma and organophosphate poisoning. ## Key points - Synthesis: choline acetyltransferase joins choline and acetyl-CoA in the nerve terminal; choline uptake is the rate-limiting step. - Storage and release: acetylcholine is packed into vesicles and released when calcium enters the terminal; botulinum toxin blocks this release. - Breakdown: acetylcholinesterase in the synaptic cleft hydrolyses acetylcholine to choline and acetate within milliseconds. - Nicotinic receptors are ligand-gated ion channels (ganglia, adrenal medulla, skeletal muscle end plate); muscarinic receptors are G protein-coupled (organs, glands, smooth muscle, heart, brain). - Cholinesterase inhibitors (neostigmine, pyridostigmine, physostigmine, organophosphates) raise acetylcholine at every cholinergic site. ## The life cycle and its drugs - Choline uptake into the terminal (blocked experimentally by hemicholinium) - Synthesis by choline acetyltransferase - Vesicular storage (vesicular acetylcholine transporter) - Calcium-dependent release: blocked by botulinum toxin, used therapeutically for spasticity, dystonia and some bladder disorders - Receptor action: agonists (pilocarpine, bethanechol), antagonists (atropine, neuromuscular blockers) - Breakdown by acetylcholinesterase: inhibited by neostigmine, pyridostigmine, physostigmine, donepezil and organophosphate insecticides ## Nicotinic and muscarinic receptors Nicotinic receptors open a cation channel within milliseconds; the muscle type (at the end plate) and the neuronal type (in ganglia and brain) differ, which is why neuromuscular blockers paralyse muscle without blocking ganglia at usual doses. Muscarinic receptors act through G proteins: M1, M3 and M5 through Gq, M2 and M4 through Gi. Atropine and scopolamine block muscarinic receptors; nicotine stimulates nicotinic ones. ## Too much and too little acetylcholine - Excess (organophosphate or carbamate poisoning, cholinesterase inhibitor overdose): muscarinic signs (salivation, tearing, urination, diarrhoea, bronchorrhoea, bradycardia, small pupils) plus nicotinic signs (fasciculations, weakness, paralysis) - Treatment of organophosphate poisoning: atropine for muscarinic effects; pralidoxime can reactivate the enzyme if given before ageing - Deficit (antimuscarinic toxicity): hot, dry, flushed skin, dilated pupils, tachycardia, urinary retention, confusion ## Clinical uses - Myasthenia gravis: pyridostigmine increases acetylcholine at end plates with fewer receptors - Reversal of non-depolarising block: neostigmine, given with an antimuscarinic to blunt bradycardia and secretions - Glaucoma and dry mouth: pilocarpine - Alzheimer's disease: central cholinesterase inhibitors - Bradycardia, preoperative secretions, poisoning: atropine ## Memory aid Muscarinic excess drains the body from top to bottom: tears, saliva, sweat, bronchial mucus, vomit, diarrhoea and urine, with slow heart and pinpoint pupils. ## Test yourself Think of the answer, then tap the question to see it. ## Where in the body are nicotinic receptors found? In autonomic ganglia, the adrenal medulla, the skeletal muscle end plate and the brain. ## How does botulinum toxin cause weakness? It blocks the release of acetylcholine from nerve terminals, so the muscle receives no signal. ## Why is atropine given in organophosphate poisoning, and what does it not fix? It blocks muscarinic receptors and reverses secretions, bronchospasm and bradycardia; it does not reverse nicotinic muscle weakness or paralysis. ## Why is neostigmine given with an antimuscarinic when reversing a neuromuscular block? Neostigmine raises acetylcholine at muscarinic sites too; the antimuscarinic prevents bradycardia, secretions and bronchospasm. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/topics/cholinergic-transmission/) ## Related classes - [Muscarinic (cholinergic) agonists](https://durgical.com/en/pharmacology/classes/muscarinic-agonists/) - [Antimuscarinics (anticholinergics)](https://durgical.com/en/pharmacology/classes/antimuscarinics/) - [Cholinesterase inhibitors](https://durgical.com/en/pharmacology/classes/cholinesterase-inhibitors/) - [Neuromuscular blockers](https://durgical.com/en/pharmacology/classes/neuromuscular-blockers/) - [Neuromuscular block reversal agents](https://durgical.com/en/pharmacology/classes/neuromuscular-block-reversal-agents/) ## Example drugs - [Atropine](https://durgical.com/en/pharmacology/atropine/) - [Pilocarpine](https://durgical.com/en/pharmacology/pilocarpine/) - [Bethanechol](https://durgical.com/en/pharmacology/bethanechol/) - [Neostigmine](https://durgical.com/en/pharmacology/neostigmine/) - [Pyridostigmine](https://durgical.com/en/pharmacology/pyridostigmine/) - [Physostigmine](https://durgical.com/en/pharmacology/physostigmine/) - [Varenicline](https://durgical.com/en/pharmacology/varenicline/) - [Suxamethonium](https://durgical.com/en/pharmacology/suxamethonium/) - [Rocuronium](https://durgical.com/en/pharmacology/rocuronium/) - [Pralidoxime](https://durgical.com/en/pharmacology/pralidoxime/) [← All of pharmacology](https://durgical.com/en/pharmacology/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [15.1 Divisions of the Autonomic Nervous System](https://openstax.org/books/anatomy-and-physiology-2e/pages/15-1-divisions-of-the-autonomic-nervous-system) (OpenStax (Rice University), 2022); [15.4 Drugs that Affect the Autonomic System](https://openstax.org/books/anatomy-and-physiology-2e/pages/15-4-drugs-that-affect-the-autonomic-system) (OpenStax (Rice University), 2022); [10.2 Skeletal Muscle](https://openstax.org/books/anatomy-and-physiology-2e/pages/10-2-skeletal-muscle) (OpenStax (Rice University), 2022). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/topics/cholinergic-transmission/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/topics/cholinergic-transmission/