Exploring What are the effects of cholinergic receptor blockade?

October 7, 2025 •

5 min read

Over 600 medications, including antidepressants and antihistamines, have some degree of anticholinergic activity, which can lead to significant side effects from cholinergic receptor blockade. Understanding these effects is crucial for managing medication risks and recognizing symptoms of toxicity.

Quick Summary

Blocking cholinergic receptors, which utilize the neurotransmitter acetylcholine, produces diverse effects across the central nervous system, heart, muscles, and glands. These effects stem from inhibiting muscarinic and nicotinic receptors and can manifest as blurred vision, dry mouth, cognitive impairment, or muscle weakness.

Key Points

Muscarinic Blockade: Inhibits the "rest and digest" functions of the parasympathetic nervous system, causing dry mouth, blurred vision, constipation, urinary retention, and tachycardia.
Central Nervous System Effects: Lipophilic anticholinergics can cross the blood-brain barrier, leading to cognitive impairment, confusion, delirium, and hallucinations, especially in the elderly.
Nicotinic Blockade: Prevents signals from motor nerves to skeletal muscles, resulting in muscle weakness and flaccid paralysis, which can cause respiratory failure in high doses.
Anticholinergic Toxicity: Overdose of muscarinic blockers leads to anticholinergic toxidrome, characterized by hyperthermia, flushed skin, dilated pupils, delirium, and urinary retention.
Therapeutic Uses: Medications like scopolamine (motion sickness), ipratropium (COPD), and benztropine (Parkinson's) leverage the blocking effects of cholinergic receptors for specific treatments.
Risk Factors: Older adults are particularly susceptible to anticholinergic side effects due to age-related changes and potential polypharmacy, which increases anticholinergic burden.

The cholinergic system is a vital communication network in the body, using the neurotransmitter acetylcholine (ACh) to send signals throughout the central nervous system (CNS) and peripheral nervous system. When drugs or toxins block the receptors for ACh, the resulting cholinergic receptor blockade disrupts these signals, causing a wide array of physiological and cognitive effects. These effects differ depending on the type of receptor blocked—muscarinic or nicotinic.

Effects of Muscarinic Receptor Blockade

Muscarinic receptors are found in many tissues and organs innervated by the parasympathetic nervous system, responsible for "rest and digest" functions. When these receptors are blocked by anticholinergic medications like atropine or scopolamine, the parasympathetic response is inhibited, leading to a predictable set of symptoms often summarized by the mnemonic: "hot as a hare, dry as a bone, blind as a bat, mad as a hatter, and full as a flask".

Peripheral manifestations

Cardiovascular system: Atropine blocks muscarinic receptors in the heart, increasing the firing of the sinoatrial node and conduction through the atrioventricular node, which leads to tachycardia (increased heart rate).
Exocrine glands: Secretions are significantly reduced throughout the body. This results in dry mouth (xerostomia), dry eyes, and reduced sweating (anhidrosis). Anhidrosis can lead to hyperthermia, especially in hot environments.
Gastrointestinal tract: Blocking muscarinic receptors reduces gastrointestinal motility and secretions. This can cause constipation, delayed gastric emptying, and decreased peristalsis.
Genitourinary system: The detrusor muscle of the bladder is relaxed, and the urethral sphincter is tightened, leading to urinary retention. This is particularly problematic for men with benign prostatic hyperplasia.
Ocular system: Blockade causes mydriasis (pupil dilation) by paralyzing the sphincter pupillae muscle. It also leads to cycloplegia (paralysis of the ciliary muscle), resulting in blurred vision and impaired accommodation (the eye's ability to focus). This can increase intraocular pressure and is a concern for patients with narrow-angle glaucoma.

Central nervous system effects

For anticholinergics that can cross the blood-brain barrier (like scopolamine and some tricyclic antidepressants), central nervous system (CNS) effects can be significant.

Cognitive impairment: Muscarinic blockade can cause confusion, memory loss, and learning difficulties. This is particularly pronounced in older adults who may have lower cholinergic reserves.
Psychiatric symptoms: Higher doses can lead to agitation, delirium, and hallucinations. This explains the "mad as a hatter" symptom from the classic mnemonic, referencing the neurological effects of mercury poisoning (which involves anticholinergic symptoms).

Effects of Nicotinic Receptor Blockade

Nicotinic receptors are a different class of cholinergic receptors primarily located at the neuromuscular junction and in autonomic ganglia. Blockade of these receptors affects skeletal muscle and autonomic function.

Neuromuscular junction: This blockade prevents the transmission of signals from motor neurons to skeletal muscles. The effect is dose-dependent, ranging from muscle weakness to complete flaccid paralysis. This is the mechanism by which neuromuscular blocking agents, like pancuronium and vecuronium, are used during surgery to induce muscle relaxation. Overdose can lead to respiratory failure due to paralysis of the diaphragm.
Autonomic ganglia: Nicotinic receptors in both sympathetic and parasympathetic ganglia can be blocked, leading to a complex and unpredictable mix of effects on blood pressure and heart rate. Blockade of ganglionic transmission can cause orthostatic hypotension due to reduced sympathetic outflow to blood vessels.
Central nervous system: Nicotinic receptors in the brain play a role in cognitive processing and reward pathways. Blockade can contribute to cognitive dysfunction and is known to alter the reinforcing effects of nicotine.

Comparison of Muscarinic vs. Nicotinic Blockade

The table below outlines the key differences in the effects of muscarinic and nicotinic cholinergic receptor blockade, helping to distinguish between the two mechanisms.


Feature	Muscarinic Blockade	Nicotinic Blockade
Target Receptors	Muscarinic (M1-M5) receptors on smooth muscle, glands, and CNS.	Nicotinic receptors at neuromuscular junctions and autonomic ganglia.
Key Symptoms	Dry mouth, dilated pupils, blurred vision, constipation, urinary retention, tachycardia, confusion, delirium.	Muscle weakness, fasciculations, flaccid paralysis, effects on blood pressure.
Primary Effect	Inhibition of the parasympathetic nervous system and CNS function.	Inhibition of skeletal muscle contraction and ganglionic autonomic transmission.
Prominent Location	Glands, smooth muscle, heart, CNS (for lipophilic agents).	Skeletal muscle motor endplates, autonomic ganglia, CNS.
Relevance	Commonly associated with anticholinergic syndrome and side effects of many medications.	Primarily used for therapeutic muscle relaxation during surgery; high doses can cause respiratory paralysis.
Mnemonic	"Hot as a hare, dry as a bone, blind as a bat, mad as a hatter, full as a flask".	No common mnemonic; effects are typically paralysis-focused.

Therapeutic applications and risks

Cholinergic blocking agents are used therapeutically to treat various conditions by leveraging their specific effects. For instance, muscarinic antagonists like ipratropium are inhaled to cause bronchodilation in chronic obstructive pulmonary disease (COPD). Scopolamine patches are used to prevent motion sickness and postoperative nausea. In Parkinson's disease, anticholinergics like benztropine help reduce tremor by rebalancing CNS cholinergic and dopaminergic activity. Neuromuscular blocking agents, which target nicotinic receptors, are indispensable in modern surgery.

However, these medications carry risks, especially in susceptible populations. Older adults are particularly vulnerable to the cognitive side effects of anticholinergics due to decreased cholinergic reserves. Combining medications with anticholinergic effects, known as the anticholinergic burden, can increase the risk of adverse events like delirium and falls. Overdose of cholinergic blockers, whether intentional or accidental, can lead to severe toxicity, requiring immediate medical intervention. For example, severe muscarinic blockade can cause a life-threatening anticholinergic toxidrome. Excessive nicotinic blockade, as seen in certain poisonings, can cause flaccid paralysis and fatal respiratory failure.

Conclusion

The effects of cholinergic receptor blockade are widespread and can profoundly impact multiple organ systems, from the heart and lungs to the brain and digestive tract. These effects are a direct consequence of inhibiting the neurotransmitter acetylcholine at either muscarinic or nicotinic receptor sites. While these agents provide significant therapeutic benefits for specific conditions, their use requires careful consideration of potential side effects, particularly cognitive impairment in the elderly and the risk of toxicity in overdose situations. The diverse range of clinical applications and risks associated with cholinergic receptor blockade underscores the intricate role of the cholinergic system in maintaining bodily function.

For more detailed information on specific anticholinergic drugs, resources like StatPearls offer extensive overviews and clinical guidance.

Frequently Asked Questions

Muscarinic receptor blockade affects parasympathetic functions like secretion and smooth muscle contraction, leading to effects such as dry mouth and blurred vision. Nicotinic receptor blockade primarily affects skeletal muscle and autonomic ganglia, causing muscle weakness and blood pressure changes.

Yes. Blockade of muscarinic receptors in the heart can cause tachycardia, or an increased heart rate. Atropine, a well-known anticholinergic, is used clinically to treat bradycardia (a slow heart rate).

Some anticholinergic medications, particularly those that can cross the blood-brain barrier, block muscarinic receptors in the central nervous system. This interferes with cognitive processes involving acetylcholine and can cause memory impairment, confusion, and delirium.

Yes, older adults are more susceptible to the adverse effects of anticholinergic drugs, especially cognitive impairment, confusion, and delirium. This is partly due to a decreased cholinergic reserve with age.

Anticholinergic toxidrome is a toxic state caused by an overdose of anticholinergic agents. Symptoms are often remembered by the phrase "hot as a hare, dry as a bone, blind as a bat, mad as a hatter, and full as a flask," describing hyperthermia, dry skin, blurred vision, delirium, and urinary retention.

Muscle paralysis is caused by the blockade of nicotinic receptors at the neuromuscular junction. This prevents acetylcholine from signaling the muscles to contract, leading to muscle weakness and potentially life-threatening flaccid paralysis.

Many drugs, even those not primarily designed as anticholinergics, can have these effects. Examples include some antihistamines (like diphenhydramine), tricyclic antidepressants, and medications used for urinary incontinence and Parkinson's disease.