What Drugs Affect Acetylcholine? A Comprehensive Guide

October 12, 2025 •

4 min read

Approximately 50% of older adults use at least one medication with anticholinergic properties, which block the neurotransmitter acetylcholine [1.7.4]. This highlights the widespread use of medications that answer the question: 'What drugs affect acetylcholine?', a critical topic in both medicine and patient awareness.

Quick Summary

Drugs affecting acetylcholine are broadly categorized as those that enhance its effects (cholinergics) and those that block its action (anticholinergics). These medications have diverse therapeutic uses and significant side effect profiles.

Key Points

Two Main Classes: Drugs affecting acetylcholine are either cholinergic (enhancing effects) or anticholinergic (blocking effects) [1.3.3].
Cholinergic Mechanisms: These drugs either directly activate acetylcholine receptors or inhibit the enzyme that breaks acetylcholine down [1.3.2].
Anticholinergic Mechanism: These drugs work by blocking acetylcholine from binding to its muscarinic receptors [1.2.2].
Therapeutic Uses: Cholinergics are used for Alzheimer's and myasthenia gravis, while anticholinergics treat conditions like COPD and overactive bladder [1.4.3, 1.5.6].
Opposing Side Effects: Cholinergic side effects include diarrhea and increased saliva, while anticholinergics cause dry mouth and constipation [1.4.1, 1.2.1].
Risk in Elderly: Anticholinergic drugs pose a significant risk of confusion, falls, and dementia in older adults [1.7.2].
Common OTC Example: The first-generation antihistamine diphenhydramine (Benadryl) has strong anticholinergic properties [1.2.1].

The Role of Acetylcholine in the Body

Acetylcholine (ACh) was the first neurotransmitter to be discovered and is a crucial chemical messenger in both the central and peripheral nervous systems [1.6.2, 1.6.6]. In the peripheral nervous system, ACh is essential for muscle contraction at the neuromuscular junction, activating all voluntary movements [1.6.4]. It is also a key neurotransmitter in the autonomic nervous system, regulating involuntary functions of the parasympathetic (rest-and-digest) system, such as heart rate, digestion, and glandular secretions [1.6.1, 1.6.3]. Within the brain, ACh plays a vital role in arousal, attention, learning, and memory [1.6.2]. Given its wide-ranging functions, medications that modulate acetylcholine levels can have profound and diverse effects on the body.

Drugs That Increase Acetylcholine (Cholinergics)

Cholinergic drugs, also known as parasympathomimetics, enhance the effects of acetylcholine [1.3.3]. They work in two primary ways: by directly stimulating ACh receptors or by preventing the breakdown of acetylcholine in the synapse [1.3.2].

Direct-Acting Cholinergic Agonists

These drugs bind directly to and activate acetylcholine receptors (both muscarinic and nicotinic) [1.3.3]. They mimic the natural action of acetylcholine.

Examples: Bethanechol is used to treat urinary retention by stimulating bladder muscle contraction [1.3.6]. Pilocarpine is used to treat glaucoma by constricting the pupil and to alleviate dry mouth in conditions like Sjögren's syndrome [1.3.6]. Cevimeline is another agent used for dry mouth [1.3.1].
Therapeutic Uses: Primarily used for promoting urinary excretion, increasing gastrointestinal motility, and in ophthalmology to reduce intraocular pressure [1.3.3].
Side Effects: Because they amplify the "rest-and-digest" functions, side effects can include increased salivation, sweating, diarrhea, abdominal cramps, and blurred vision [1.4.2].

Indirect-Acting Agents (Acetylcholinesterase Inhibitors)

These drugs work by inhibiting acetylcholinesterase (AChE), the enzyme responsible for breaking down acetylcholine in the synaptic cleft [1.3.3, 1.4.2]. By blocking this enzyme, they increase the concentration and duration of action of naturally released ACh [1.4.6].

Examples: Donepezil (Aricept), Rivastigmine (Exelon), and Galantamine (Reminyl) are commonly prescribed to manage symptoms of mild to moderate Alzheimer's disease by increasing cholinergic activity in the brain [1.2.1, 1.4.4]. Pyridostigmine and Neostigmine are used to treat myasthenia gravis, an autoimmune disorder characterized by muscle weakness [1.3.1, 1.4.3].
Therapeutic Uses: Primarily for Alzheimer's disease, other forms of dementia, and myasthenia gravis [1.2.3, 1.4.3]. They can also be used to reverse the effects of certain muscle relaxants after surgery [1.4.3].
Side Effects: Common adverse effects result from excessive cholinergic stimulation and can be remembered by the mnemonic SLUDGE: Salivation, Lacrimation (tearing), Urination, Diaphoresis (sweating), Gastrointestinal upset, and Emesis (vomiting) [1.4.1, 1.4.6]. Other effects include bradycardia (slow heart rate), insomnia, and muscle cramps [1.4.2, 1.4.4].

Drugs That Block Acetylcholine (Anticholinergics)

Anticholinergic drugs (also called parasympatholytics or antimuscarinics) work by blocking acetylcholine from binding to its muscarinic receptors, thereby inhibiting the effects of the parasympathetic nervous system [1.2.2].

Examples: Atropine is used to treat slow heart rate (bradycardia) and as an antidote for certain poisonings [1.5.1]. Scopolamine is effective for motion sickness [1.5.1]. Oxybutynin, Tolterodine, and Solifenacin are used to treat overactive bladder [1.5.1]. Ipratropium and Tiotropium are inhaled to treat respiratory conditions like COPD and asthma [1.5.1]. Diphenhydramine (Benadryl), an over-the-counter antihistamine, also has significant anticholinergic effects [1.2.1].
Therapeutic Uses: Anticholinergics are used for a wide variety of conditions, including overactive bladder, COPD, Parkinson's disease, motion sickness, and reducing secretions during surgery [1.5.1, 1.5.6].
Side Effects: The side effects are the opposite of cholinergic effects and include dry mouth, blurred vision, constipation, urinary retention, drowsiness, confusion, and increased heart rate [1.2.1, 1.7.2]. In older adults, these drugs are associated with an increased risk of cognitive impairment, delirium, falls, and even dementia with long-term use [1.7.2, 1.7.3].

Comparison of Cholinergic and Anticholinergic Drugs


Feature	Cholinergic Drugs (Agonists)	Anticholinergic Drugs (Antagonists)
Mechanism of Action	Mimic ACh or inhibit its breakdown (AChE inhibitors) [1.3.3]	Block muscarinic acetylcholine receptors [1.2.2]
Effect on Acetylcholine	Increases availability and effect [1.3.2]	Decreases or inhibits effect [1.2.4]
Common Examples	Donepezil (Aricept), Pilocarpine, Neostigmine [1.2.1, 1.3.1]	Atropine, Scopolamine, Oxybutynin, Diphenhydramine [1.5.1]
Therapeutic Uses	Alzheimer's disease, myasthenia gravis, glaucoma, dry mouth [1.2.3, 1.3.3]	Overactive bladder, COPD, Parkinson's, motion sickness [1.5.6]
Common Side Effects	Diarrhea, nausea, increased saliva, sweating, slow heart rate [1.4.1]	Dry mouth, blurred vision, constipation, confusion, dementia risk [1.7.2]

Conclusion

Pharmacological manipulation of the acetylcholine system offers powerful therapeutic options for a vast range of medical conditions, from dementia to overactive bladder. However, this power comes with a significant responsibility for careful management. Drugs that increase acetylcholine (cholinergics) and those that block it (anticholinergics) have opposing effects and side-effect profiles that directly reflect acetylcholine's widespread role in the body. The potential for serious adverse effects, particularly the cognitive risks associated with anticholinergics in the elderly, underscores the importance of medical supervision when using these medications [1.7.2]. Balancing the therapeutic benefits against the potential risks is a critical aspect of clinical practice.

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Frequently Asked Questions

The two main types are cholinergic drugs, which increase acetylcholine's effects, and anticholinergic drugs, which block its effects [1.3.3].

They are most commonly used to treat the cognitive symptoms of Alzheimer's disease and dementia, as well as to improve muscle strength in myasthenia gravis [1.2.1, 1.4.3].

Common side effects include dry mouth, blurred vision, constipation, urinary retention, drowsiness, and confusion [1.2.1]. The mnemonic 'blind as a bat, dry as a bone, red as a beet, hot as a hare, mad as a hatter' is often used [1.9.2].

Yes, many common over-the-counter medications have anticholinergic properties, most notably first-generation antihistamines like diphenhydramine (Benadryl) and some sleep aids [1.2.1, 1.5.3].

In older adults, anticholinergic drugs are associated with a higher risk of adverse effects including confusion, delirium, falls, and an increased risk of developing dementia with cumulative use [1.7.2, 1.7.3].

A cholinergic crisis is a medical emergency caused by an excess of acetylcholine, often from an overdose of acetylcholinesterase inhibitor medication. Symptoms include muscle weakness, difficulty breathing, increased salivation and sweating, and gastrointestinal issues [1.8.4].

Both cause severe muscle weakness and respiratory failure. A myasthenic crisis is caused by a worsening of myasthenia gravis itself (undertreatment), while a cholinergic crisis is caused by an overdose of medication (overtreatment). An edrophonium test can differentiate them, as it improves a myasthenic crisis but worsens a cholinergic one [1.8.2].