Anticholinergic Drugs: Effects and Examples

By Dr. Zubair Khalid, DVM, MS, PhD · 2026-09-20

Anticholinergic drugs are compounds that block muscarinic acetylcholine receptors, the receptor subtype that carries most parasympathetic ("rest and digest") signals to the heart, glands, pupil, gut, and bladder. Blocking those receptors slows the heart when it is beating too fast for the clinical situation, dries secretions, dilates the pupil, and quiets gut and bladder contractions. In veterinary practice, anticholinergic drugs are used most often to prevent or treat bradycardia (slow heart rate) during anesthesia, to dry airway secretions before intubation, to counter organophosphate and carbamate poisoning, and to relieve some forms of diarrhea and urinary spasm. The class includes atropine, glycopyrrolate, hyoscine (scopolamine), and isopropamide, and each one differs in which muscarinic receptor subtypes it prefers, how long it acts, and whether it reaches the brain.

This article is educational and is not a substitute for veterinary diagnosis or treatment.

At a Glance

What "Anticholinergic" Actually Means

Acetylcholine is the neurotransmitter used by all parasympathetic postganglionic fibers and by some central nervous system pathways. It binds two families of receptors. Nicotinic receptors sit on skeletal muscle and on autonomic ganglia, and they mediate fast excitatory transmission. Muscarinic receptors sit on smooth muscle, cardiac muscle, exocrine glands, and many central neurons, and they mediate the slower, longer-lasting parasympathetic effects. Anticholinergic drugs in the sense used here are muscarinic antagonists, sometimes called antimuscarinics. They do not block nicotinic receptors at usual clinical doses, so they do not paralyze skeletal muscle.

The block is competitive and reversible. The drug occupies the orthosteric site on the muscarinic receptor, acetylcholine cannot bind, and the tissue behaves as if no parasympathetic signal arrived. The effect therefore depends on how much cholinergic tone the tissue had in the first place. A resting, well-oxygenated dog with a normal heart rate of 90 beats per minute will show little change from atropine. A dog whose heart rate has dropped to 40 beats per minute because of an opioid or a vagal reflex will respond dramatically, because the drug is removing an active brake rather than pushing the accelerator.

Atropine is the classic experimental tool for confirming muscarinic involvement in a physiological response. In a rat model of corneal and orofacial pain, atropine injected into the fourth ventricle blocked the analgesic effect of thymoquinone, which is evidence that central muscarinic signaling contributes to that effect [1]. In isolated mouse cardiomyocytes, atropine prevented carbachol-induced activation of the NLRP3 inflammasome, confirming that the muscarinic receptor mediates that inflammatory pathway [2]. In rat small intestine, atropine did not block spexin-induced contractions, which is how the investigators showed that spexin acts through galanin-2 receptors rather than muscarinic ones [3]. These are laboratory uses, but they illustrate the logic that applies clinically: if atropine abolishes a response, the response was muscarinic.

Mechanism: Competitive Blockade at Muscarinic Receptors

Receptor subtypes and what each one does

Five muscarinic receptor subtypes exist, labeled M1 through M5. M1 receptors are mainly neural, M2 receptors dominate the heart, M3 receptors drive glandular secretion and smooth muscle contraction, M4 receptors are largely central and presynaptic, and M5 receptors are central. Most veterinary anticholinergics are non-selective, meaning they block all five to some degree. That lack of selectivity explains why the side-effect profile of the class is broad and predictable.

The clinically important consequences of blocking each subtype are:

• M2 blockade in the sinoatrial and atrioventricular nodes removes vagal slowing. Heart rate rises and atrioventricular conduction improves.
• M3 blockade in salivary, lacrimal, bronchial, and sweat glands reduces secretion. The mouth and airways become dry.
• M3 blockade in the iris sphincter and ciliary muscle causes mydriasis (pupil dilation) and cycloplegia (loss of accommodation).
• M3 blockade in the detrusor muscle and gastrointestinal smooth muscle reduces contractility, producing urinary retention and ileus.
• M3 blockade in the lower esophageal sphincter and stomach reduces gastric motility and can worsen reflux.
• M1 and M4 blockade in the brain produces sedation, amnesia, and at higher doses, excitement or delirium.

Why the same drug dries the mouth and speeds the heart

Every muscarinic effect is a loss of a parasympathetic brake. The tissue with the highest resting parasympathetic tone shows the largest change. Salivary glands have constant high tone, so dryness appears quickly. The heart has moderate vagal tone at rest, so heart rate rises modestly in a healthy animal and dramatically in one with high vagal tone. The gut has high tone after a meal, so motility falls noticeably. This is why the same injection that controls bradycardia in an anesthetized dog also produces a dry mouth and a quiet abdomen.

Central versus peripheral effects

The single most useful distinction for choosing between atropine and glycopyrrolate is whether the molecule crosses the blood-brain barrier. Atropine is a tertiary amine. It is uncharged at physiological pH, lipid-soluble, and freely enters the central nervous system. That is why atropine can cause central excitation, disorientation, and at high doses, seizures, and why it is used experimentally to probe central cholinergic pathways [1][4]. Glycopyrrolate is a quaternary ammonium compound. It carries a permanent positive charge, is poorly lipid-soluble, and essentially does not cross the blood-brain barrier at clinical doses. Its effects are therefore confined to the periphery. Hyoscine sits between the two: it is a tertiary amine and crosses into the brain, which is why it is used for motion sickness and produces more sedation than atropine. Isopropamide is quaternary and peripheral, like glycopyrrolate.

This distinction matters in practice. An animal with central nervous system signs from organophosphate poisoning needs a drug that reaches the brain, so atropine is the logical choice. An animal that simply needs its heart rate supported during anesthesia is better served by glycopyrrolate, because it will not add central excitation on top of an anesthetic.

The Class Table: Receptor Selectivity, Indications, Onset, Duration, and Adverse Effects

Onset and duration figures vary with route, species, and dose, and the table gives the general pattern rather than a fixed rule. The one consistent rule is that glycopyrrolate outlasts atropine and atropine outlasts hyoscine after equivalent routes.

Labeled and Accepted Uses in Veterinary Medicine

Pre-anesthetic bradycardia

Bradycardia during anesthesia comes from several sources. Opioids increase vagal tone. Alpha-2 agonists such as xylazine and dexmedetomidine cause a reflex slowing. Traction on the eye, larynx, or viscera triggers vagal reflexes. Anticholinergics are given before or during these events to keep heart rate and cardiac output adequate.

The evidence for benefit is clearest when cardiac output is genuinely compromised. In anesthetized dogs given ephedrine, heart rate fell significantly in the saline-pretreated group, two dogs developed bradycardia below 50 beats per minute, and one developed atrioventricular block. Dogs pretreated with atropine at 0.04 mg/kg intravenously showed a rise in heart rate instead, and no tachycardia occurred [5]. In horses anesthetized with xylazine and ketamine, pretreatment with glycopyrrolate at 2.5 micrograms per kilogram intravenously produced significantly higher heart rate, arterial blood pressures, cardiac index, oxygen delivery, and mixed venous oxygen tension than saline, with less tissue oxygen extraction [6]. In buffalo calves, a glycopyrrolate-xylazine-propofol protocol kept heart rate elevated through anesthesia without significant change in rectal temperature [7]. In dogs sedated with hydromorphone, acepromazine, dexmedetomidine, and glycopyrrolate at 0.02 mg/kg intramuscularly, cardiac index was significantly higher than with dexmedetomidine-containing combinations that lacked glycopyrrolate [8].

The counterpoint is that anticholinergics are not automatically beneficial. Giving atropine to a dog that is already tachycardic because of pain or hypovolemia will worsen the tachycardia and increase myocardial oxygen demand without improving output. The drug treats the rate, not the cause.

Organophosphate and carbamate toxicity

Organophosphates and carbamates inhibit acetylcholinesterase, so acetylcholine accumulates at every cholinergic synapse. The muscarinic signs include profuse salivation, lacrimation, urination, diarrhea, bronchoconstriction, and bradycardia, often remembered as the DUMBELS pattern. Atropine reverses these muscarinic signs and is the standard first-line antidote for the muscarinic component. It does not reverse the nicotinic signs (muscle fasciculations, weakness, respiratory paralysis), which require an oxime such as pralidoxime when the poison is an organophosphate rather than a carbamate. Atropine is chosen over glycopyrrolate here because central cholinergic excess contributes to seizures and coma, and only the tertiary amine reaches the brain.

Diarrhea and gastrointestinal spasm

Anticholinergics reduce gut motility and secretion, so they can reduce the frequency of some diarrheas. The trade-off is that slowing a gut that is trying to expel a pathogen or toxin can worsen the underlying problem. In horses, N-butylscopolammonium bromide, a quaternary anticholinergic, caused bolus retention and thoracic inlet contrast pooling during videofluoroscopic swallow studies, and multiple horses retained barium after the drug and after xylazine [9]. That is a direct demonstration that anticholinergic effects on swallowing and esophageal transit are real and measurable. In horses anesthetized with xylazine and ketamine, both saline- and glycopyrrolate-treated groups had complete loss of intestinal motility [6]. The clinical lesson is that anticholinergics should be used for diarrhea only when the diarrhea is driven by hypermotility and not by an infectious or obstructive cause.

Ophthalmic use

Topical anticholinergics dilate the pupil for fundic examination and for some intraocular procedures. In guinea pigs, 1% atropine, 1% cyclopentolate, and 1% tropicamide all produced significant pupil dilation, while 2% pilocarpine constricted the pupil [10]. That study also showed age-dependent differences in pupil dynamics, with both 2-week-old and 12-week-old guinea pigs constricting strongly under direct illumination. The practical point is that mydriatic response varies with age and species, so a pupil that dilates poorly in a young animal is not necessarily a drug failure.

Urinary and biliary spasm

Anticholinergics relax the detrusor muscle and can relieve some forms of urinary spasm, but the same action can precipitate urinary retention in an animal that is already struggling to void. They are also used to relax biliary and ureteral smooth muscle in some species, though the evidence base is thinner than for cardiac and gastrointestinal uses.

What Anticholinergics Do Not Cover

Anticholinergics do not reverse nicotinic signs of organophosphate poisoning, including muscle fasciculations and respiratory muscle paralysis. They do not treat the underlying cause of bradycardia, so an animal with bradycardia from hypothermia, hyperkalemia, or a conduction-system disease needs that cause addressed. They do not kill bacteria, so they have no role in treating infectious diarrhea beyond symptom control. They do not reverse opioid-induced respiratory depression. In a rat study, atropine given after morphine did not change respiratory frequency, tidal volume, minute ventilation, or most timing parameters, though it did reduce some morphine-induced changes in expiratory flow [4]. A related study found that atropine alone increased breathing frequency and lowered tidal volume [11]. The takeaway is that anticholinergics are not respiratory stimulants and should not be used as such.

Species Differences That Change the Risk

Rabbits and guinea pigs are the species where anticholinergic effects on the gut are most dangerous. Both are hindgut fermenters with continuous cecal and colonic motility, and both depend on that motility to move ingesta and maintain a healthy bacterial population. A drug that stops gut motility in a rabbit can trigger stasis, gas accumulation, and a cascade that is difficult to reverse. The same dose that helps a dog's heart rate can be catastrophic in a rabbit. Anticholinergics should be used in rabbits and guinea pigs only when the indication is strong and the alternative is worse, and gut motility should be monitored closely afterward.

Horses are also sensitive, though for different reasons. Equine gut motility is continuous and the cecum and colon are large fermentation chambers. Loss of motility predisposes to impaction and gas colic. The videofluoroscopic study in horses showed that anticholinergic treatment caused bolus retention and contrast pooling, which is direct evidence of impaired transit [9]. The xylazine-ketamine study showed complete loss of intestinal motility in both treatment groups [6]. In horses, anticholinergics are usually reserved for specific indications such as reducing airway secretions or treating certain colic presentations, and they are not given casually.

Cats are more sensitive than dogs to the central excitatory effects of atropine, and they are also more prone to anticholinergic ileus and urinary retention. Dogs tolerate atropine reasonably well but can still show marked tachycardia and dry mouth. Guinea pigs show robust mydriatic responses to topical anticholinergics, as the pupillary study demonstrated [10], but that same sensitivity applies to systemic effects on the gut.

How Anticholinergics Are Given

Anticholinergics are given by several routes, and the route changes both the onset and the duration.

Intravenous injection produces the fastest onset, often within a minute, and is used for acute bradycardia and for organophosphate poisoning. Intramuscular and subcutaneous routes are used for premedication and produce onset over several minutes. Oral administration is used for chronic antispasmodic therapy, with isopropamide being the main oral agent in this class. Ophthalmic drops are used for mydriasis and act locally with minimal systemic absorption, though systemic effects can still occur if the drops drain through the nasolacrimal duct and are swallowed.

Transdermal hyoscine patches are used in some species for motion sickness and nausea, but absorption is variable and the patch must be handled carefully because the drug is potent.

Side Effects and What to Do About Them

The adverse-effect checklist for this class is predictable because it is a direct extension of the mechanism. Every anticholinergic effect is a parasympathetic function that has been switched off.

• Tachycardia. Heart rate rises. In most cases this is the intended effect. If the rate becomes excessive, the drug should be stopped and the animal reassessed. The atropine-ephedrine study in dogs showed that atropine pretreatment prevented the bradycardia and atrioventricular block seen with ephedrine alone, and no tachycardia occurred in that study [5], but higher doses or different species can produce marked tachycardia.
• Dry mouth and dry airways. Salivary and bronchial secretions fall. This is often desirable before intubation but can make swallowing uncomfortable afterward. In buffalo calves, muzzle and nostrils became dry after glycopyrrolate administration [7].
• Mydriasis and photophobia. The pupil dilates and cannot constrict to bright light. Animals may squint or avoid bright areas. This resolves as the drug wears off.
• Ileus and constipation. Gut motility falls. In horses, anticholinergic treatment caused bolus retention and contrast pooling [9], and glycopyrrolate-treated horses had complete loss of intestinal motility after xylazine-ketamine anesthesia [6]. In small animals, ileus presents as a quiet abdomen, reduced appetite, and reduced fecal output. Any animal that develops these signs after an anticholinergic should be evaluated promptly.
• Urinary retention. The detrusor muscle relaxes and the sphincter tone is unopposed. Animals may strain to urinate or produce no urine. This is most dangerous in male cats with urethral obstruction and in any animal with pre-existing urinary disease.
• Central excitation. Atropine and hyoscine can cause restlessness, disorientation, and at high doses, seizures. This is because they cross the blood-brain barrier. Glycopyrrolate and isopropamide do not cause this at usual doses.
• Hyperthermia. Reduced sweating and salivation impair heat loss, and central excitation increases heat production. This is a concern in hot environments and in animals with thick coats.

If any of these effects appear, the first step is to stop the drug and assess the animal. Most effects are dose-dependent and reversible as the drug is cleared. There is no specific antidote for anticholinergic overdose in veterinary medicine, so treatment is supportive and directed at the specific problem, such as fluid therapy for tachycardia, catheterization for urinary retention, and cooling for hyperthermia.

Which Animals Should Not Receive Anticholinergics

Anticholinergics should be avoided or used with extreme caution in animals with:

• Tachycardia or tachyarrhythmia of any cause, because the drug will worsen it.
• Glaucoma or a history of narrow-angle glaucoma, because mydriasis can precipitate an acute attack.
• Ileus, gastric dilation, or any condition where gut motility is already compromised.
• Urinary retention or urethral obstruction, because the drug will worsen it.
• Myasthenia gravis, because anticholinergics can mask or worsen the muscarinic component of a cholinergic crisis.
• Severe hepatic or renal disease, because clearance may be prolonged.
• Rabbits and guinea pigs with any gastrointestinal signs, because of the high risk of stasis.

Interactions With Other Drugs

Anticholinergics interact with other drugs in predictable ways. They add to the effects of other anticholinergics, so giving atropine and glycopyrrolate together is rarely justified. They oppose the effects of cholinergic agonists such as bethanechol, pilocarpine, and neostigmine, so they should not be given at the same time as those drugs unless the intent is specifically to block them. They can worsen the tachycardia caused by sympathomimetics such as ephedrine, though the atropine-ephedrine study in dogs showed that atropine pretreatment actually prevented the bradycardia and atrioventricular block seen with ephedrine alone [5]. They can reduce the absorption of orally administered drugs by slowing gastric emptying. They can add to the central nervous system depression caused by anesthetics and sedatives, particularly atropine and hyoscine.

How Anticholinergics Compare With Alternatives

The main alternatives to anticholinergics for bradycardia are direct sympathomimetics and chronotropes. Ephedrine raises heart rate by releasing norepinephrine, and it also raises blood pressure. The atropine-ephedrine study showed that the two drugs interact in a way that prevents the reflex bradycardia seen with ephedrine alone [5]. Atropine is preferred when the bradycardia is vagally mediated, and ephedrine is preferred when the bradycardia is accompanied by hypotension from vasodilation.

For diarrhea, the alternatives are fluid therapy, dietary management, antimicrobials when indicated, and drugs that act on opioid receptors in the gut such as loperamide. Anticholinergics are generally reserved for hypermotility-driven diarrhea and are not first-line therapy.

For organophosphate poisoning, atropine is the specific muscarinic antidote and there is no substitute. Oximes such as pralidoxime are used in addition to atropine to reactivate acetylcholinesterase at nicotinic synapses.

For mydriasis, topical atropine, cyclopentolate, and tropicamide are all effective, with tropicamide producing the shortest duration and atropine the longest. The guinea pig study confirmed that all three dilate the pupil, while pilocarpine constricts it [10].

Questions to Ask a Veterinarian

Before an anticholinergic is given, the following questions help clarify the plan:

1. What is the specific reason for this drug in my animal?
2. Is the bradycardia vagally mediated, or is there another cause that needs treatment?
3. Would glycopyrrolate be safer than atropine for my animal, given the central effects?
4. Does my animal have any condition that makes anticholinergics dangerous, such as glaucoma, ileus, or urinary obstruction?
5. What signs should I watch for at home after the drug is given?
6. How long will the effects last, and when should I expect my animal to return to normal?
7. Are there other drugs my animal is taking that could interact?
8. If my animal is a rabbit or guinea pig, is there a safer alternative?

Clinical Relevance, Limitations and Common Mistakes

Anticholinergics are among the most useful drugs in veterinary emergency and anesthesia practice, and they are also among the easiest to misuse. The clinical relevance is highest in three situations: vagally mediated bradycardia during anesthesia, organophosphate and carbamate poisoning, and ophthalmic mydriasis. In each of these, the drug addresses a specific physiological problem and the benefit is measurable. The atropine-ephedrine study in dogs, the glycopyrrolate studies in horses and buffalo calves, and the guinea pig pupillary study all show measurable, reproducible effects that clinicians can rely on [10][5][7][6].

The limitations are equally clear. Anticholinergics do not treat causes, only effects. They do not reverse nicotinic signs of organophosphate poisoning, they do not stimulate respiration, and they do not kill pathogens. Their side effects are predictable extensions of their mechanism, and in some species those side effects are more dangerous than the problem being treated. Rabbits and guinea pigs are the clearest example, where gut stasis can be fatal. Horses are a close second, where loss of motility can lead to impaction.

The most common mistakes are giving an anticholinergic to an animal that is already tachycardic, using atropine when glycopyrrolate would avoid central effects, giving an anticholinergic to a rabbit or guinea pig without a strong indication, and failing to monitor gut motility after administration. A less common but serious mistake is using an anticholinergic to treat diarrhea in an animal with an infectious or obstructive cause, where slowing the gut worsens the outcome.

Individual animals vary in their response to anticholinergics, and the right drug, dose, and route depend on the species, the indication, and the animal's overall condition. A veterinarian who knows the animal's history is the only person who can make that judgment safely.

Frequently Asked Questions

What are anticholinergic drugs used for in animals?

Anticholinergic drugs are used to treat or prevent bradycardia during anesthesia, to dry airway secretions before intubation, to reverse the muscarinic signs of organophosphate and carbamate poisoning, to dilate the pupil for eye examination, and to reduce some forms of diarrhea and urinary spasm.

How do anticholinergic drugs work?

They competitively block muscarinic acetylcholine receptors, so acetylcholine released by parasympathetic nerves cannot bind. The tissue behaves as if no parasympathetic signal arrived, which slows the heart when it is beating too fast, reduces secretions, dilates the pupil, and quiets the gut and bladder.

What is the difference between atropine and glycopyrrolate?

Atropine crosses the blood-brain barrier and can cause central excitation, while glycopyrrolate does not cross it and stays in the periphery. Glycopyrrolate also lasts longer than atropine. The choice depends on whether central effects are wanted or should be avoided.

Why are rabbits and guinea pigs especially sensitive to anticholinergics?

Rabbits and guinea pigs depend on continuous gut motility to move ingesta and maintain a healthy gut bacterial population. Anticholinergics can stop that motility and trigger stasis, gas accumulation, and a cascade that is difficult to reverse.

Can anticholinergics be used to treat diarrhea in dogs?

They can reduce diarrhea that is driven by hypermotility, but they should not be used when the diarrhea is caused by an infection or an obstruction, because slowing the gut can worsen the underlying problem. Fluid therapy and treatment of the cause are more important.

Do anticholinergics help with organophosphate poisoning?

Yes, atropine reverses the muscarinic signs such as salivation, lacrimation, urination, diarrhea, bronchoconstriction, and bradycardia. It does not reverse the nicotinic signs such as muscle fasciculations and respiratory paralysis, which require an oxime such as pralidoxime when the poison is an organophosphate.

What are the most common side effects of anticholinergics?

The most common side effects are tachycardia, dry mouth, dilated pupils, reduced gut motility, and urinary retention. Atropine and hyoscine can also cause central excitation because they reach the brain.

What should I do if my animal shows side effects after an anticholinergic?

Stop the drug and contact your veterinarian. Most effects are dose-dependent and reversible, but tachycardia, ileus, and urinary retention can be serious. Treatment is supportive and directed at the specific problem.

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