Atropine is a tropane alkaloid and

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...

medication used to treat certain types of

nerve agent Nerve agents, sometimes also called nerve gases, are a class of organic chemistry, organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (ACh ...

and

pesticide poisoning A pesticide poisoning occurs when pesticides, chemicals intended to control a pest, affect non-target organisms such as humans, wildlife, plants, or bees. There are three types of pesticide poisoning. The first of the three is a single and sho ...

s as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given intravenously or by injection into a muscle. Eye drops are also available which are used to treat uveitis and early amblyopia. The intravenous solution usually begins working within a minute and lasts half an hour to an hour. Large doses may be required to treat some poisonings. Common

side effects In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually used ...

include dry mouth, abnormally large pupils,

urinary retention Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include urinary incont ...

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...

, and a fast heart rate. It should generally not be used in people with closed-angle glaucoma. While there is no evidence that its use during pregnancy causes birth defects, this has not been well studied so sound clinical judgment should be used. It is likely safe during breastfeeding. It is an

antimuscarinic A muscarinic acetylcholine receptor antagonist, also simply known as a muscarinic antagonist or as an antimuscarinic agent, is a type of anticholinergic drug that blocks the activity of the muscarinic acetylcholine receptors (mAChRs). The muscarin ...

(a type of anticholinergic) that works by inhibiting the

parasympathetic nervous system The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The autonomic nervous system is responsible for regulat ...

. Atropine occurs naturally in a number of plants of the

nightshade family Solanaceae (), commonly known as the nightshades, is a family of flowering plants in the order Solanales. It contains approximately 2,700 species, several of which are used as agricultural crops, medicinal plants, and ornamental plants. Many me ...

, including deadly nightshade (''Atropa belladonna''), jimsonweed (''Datura stramonium''), mandrake (''Mandragora officinarum'') and angel's trumpet (''Brugmansia''). Atropine was first isolated in 1833. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication.

Medical uses

Eyes

Topical atropine is used as a

cycloplegic Cycloplegia is paralysis of the ciliary muscle of the Human eye, eye, resulting in a loss of accommodation (eye), accommodation. Because of the paralysis of the ciliary muscle, the curvature of the lens can no longer be adjusted to focus on near ...

, to temporarily paralyze the accommodation reflex, and as a mydriatic, to dilate the pupils. Atropine degrades slowly, typically wearing off in 7 to 14 days, so it is generally used as a therapeutic mydriatic, whereas tropicamide (a shorter-acting cholinergic antagonist) or phenylephrine (an α-adrenergic agonist) is preferred as an aid to ophthalmic examination. In refractive and accommodative amblyopia, when occlusion is not appropriate sometimes atropine is given to induce blur in the good eye. Evidence suggests that atropine penalization is just as effective as occlusion in improving visual acuity. Antimuscarinic topical medication is effective in slowing myopia progression in children; accommodation difficulties and papillae and follicles are possible side effects. All doses of atropine appear similarly effective, while higher doses have greater side effects. The lower dose of 0.01% is thus generally recommended due to fewer side effects and potential less rebound worsening when the atropine is stopped.

Heart

Injections of atropine are used in the treatment of symptomatic or unstable

bradycardia Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...

. Atropine was previously included in international resuscitation guidelines for use in cardiac arrest associated with asystole and PEA but was removed from these guidelines in 2010 due to a lack of evidence for its effectiveness. For symptomatic bradycardia, the usual dosage is 0.5 to 1 mg IV push; this may be repeated every 3 to 5 minutes, up to a total dose of 3 mg (maximum 0.04 mg/kg). Atropine is also useful in treating second-degree heart block Mobitz type 1 (Wenckebach block), and also third-degree heart block with a high Purkinje or AV-nodal escape rhythm. It is usually not effective in second-degree heart block Mobitz type 2, and in third-degree heart block with a low Purkinje or ventricular escape rhythm. Atropine has also been used to prevent a low heart rate during intubation of children; however, the evidence does not support this use.

Secretions

Atropine's actions on the parasympathetic nervous system inhibit salivary and mucous glands. The drug may also inhibit sweating via the sympathetic nervous system. This can be useful in treating

hyperhidrosis Hyperhidrosis is a medical condition in which a person exhibits excessive perspiration, sweating, more than is required for the Thermoregulation, regulation of body temperature. Although it is primarily a physical burden, hyperhidrosis can deterio ...

, and can prevent the death rattle of dying patients. Even though atropine has not been officially indicated for either of these purposes by the FDA, it has been used by physicians for these purposes.

Poisonings

Atropine acts as an

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.organophosphate poisoning by blocking the action of

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

at muscarinic receptors caused by

organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...

insecticide Insecticides are pesticides used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. The major use of insecticides is in agriculture, but they are also used in home and garden settings, i ...

s and

s, such as tabun (GA), sarin (GB), soman (GD), and VX. Troops who are likely to be attacked with chemical weapons often carry autoinjectors with atropine and oxime, for rapid injection into the muscles of the thigh. In a developed case of nerve gas poisoning, maximum atropinization is desirable. Atropine is often used in conjunction with the oxime pralidoxime chloride. Some of the nerve agents attack and destroy acetylcholinesterase by

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

, so the action of acetylcholine becomes excessive and prolonged. Pralidoxime (2-PAM) can be effective against organophosphate poisoning because it can re-cleave this phosphorylation. Atropine can be used to reduce the effect of the poisoning by blocking muscarinic acetylcholine receptors, which would otherwise be overstimulated, by excessive acetylcholine accumulation. Atropine or

diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...

can be used to treat muscarine intoxication. Atropine was added to cafeteria salt shakers in an attempt to poison the staff of

Radio Free Europe Radio Free Europe/Radio Liberty (RFE/RL) is a media organization broadcasting news and analyses in 27 languages to 23 countries across Eastern Europe, Central Asia, the Caucasus, and the Middle East. Headquartered in Prague since 1995, RFE/RL ...

during the

Cold War The Cold War was a period of global Geopolitics, geopolitical rivalry between the United States (US) and the Soviet Union (USSR) and their respective allies, the capitalist Western Bloc and communist Eastern Bloc, which lasted from 1947 unt ...

Irinotecan-induced diarrhea

Atropine has been observed to prevent or treat irinotecan induced acute diarrhea.

Side effects

Adverse reactions to atropine include ventricular fibrillation, supraventricular or ventricular tachycardia, dizziness,

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

, blurred vision, loss of balance, dilated pupils,

photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom, photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence o ...

, dry mouth and potentially extreme confusion, deliriant

hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...

s, and excitation especially among the elderly. These latter effects are because atropine can cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

. Because of the hallucinogenic properties, some have used the drug recreationally, though this is potentially dangerous and often unpleasant. In overdoses, atropine is

poison A poison is any chemical substance that is harmful or lethal to living organisms. The term is used in a wide range of scientific fields and industries, where it is often specifically defined. It may also be applied colloquially or figurati ...

ous. Atropine is sometimes added to potentially addictive drugs, particularly antidiarrhea opioid drugs such as diphenoxylate or difenoxin, wherein the secretion-reducing effects of the atropine can also aid the antidiarrhea effects. Although atropine treats

(slow heart rate) in emergency settings, it can cause paradoxical heart rate slowing when given at very low doses (less than 0.5 mg), presumably as a result of central action in the CNS. One proposed mechanism for atropine's paradoxical bradycardia effect at low doses involves blockade of inhibitory presynaptic muscarinic autoreceptors, thereby blocking a system that inhibits the parasympathetic response. Atropine is incapacitating at doses of 10 to 20 mg per person. Its LD₅₀ is estimated to be 453 mg per person (by mouth) with a probit slope of 1.8. The antidote to atropine is physostigmine or pilocarpine. A common

mnemonic A mnemonic device ( ), memory trick or memory device is any learning technique that aids information retention or retrieval in the human memory, often by associating the information with something that is easier to remember. It makes use of e ...

used to describe the physiologic manifestations of atropine overdose is: "hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter". citing J. Arena, Poisoning: Toxicology-Symptoms-Treatments, 3rd edition. Springfield, Charles C. Thomas, 1974, p 345 These associations reflect the specific changes of warm, dry skin from decreased sweating, blurry vision, decreased lacrimation, vasodilation, and central nervous system effects on muscarinic receptors, type 4 and 5. This set of symptoms is known as anticholinergic toxidrome, and may also be caused by other drugs with anticholinergic effects, such as hyoscine hydrobromide (scopolamine),

, phenothiazine

antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

s and benztropine.

Contraindications

It is generally contraindicated in people with

glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

, pyloric stenosis, or prostatic hypertrophy, except in doses ordinarily used for preanesthesia.

Chemistry

Atropine, a tropane alkaloid, is an

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

ic mixture of '' d''- hyoscyamine and ''l''-hyoscyamine, with most of its physiological effects due to ''l''-hyoscyamine, the 3(''S'')-''endo'' isomer of atropine. Its pharmacological effects are due to binding to muscarinic acetylcholine receptors. It is an antimuscarinic agent. Significant levels are achieved in the CNS within 30 minutes to 1 hour and disappear rapidly from the blood with a half-life of 2 hours. About 60% is excreted unchanged in the urine, and most of the rest appears in the urine as hydrolysis and conjugation products. Noratropine (24%), atropine-N-oxide (15%), tropine (2%), and tropic acid (3%) appear to be the major metabolites, while 50% of the administered dose is excreted as apparently unchanged atropine. No conjugates were detectable. Evidence that atropine is present as (+)-hyoscyamine was found, suggesting that stereoselective metabolism of atropine probably occurs. Effects on the iris and ciliary muscle may persist for longer than 72 hours. The most common atropine compound used in medicine is atropine sulfate (monohydrate) ()₂· H₂SO₄· H₂O, the full chemical name is 1α''H'',5α''H''-tropan-3-α-ol (±)-tropate(ester), sulfate monohydrate.

Pharmacology

In general, atropine counters the "rest and digest" activity of

gland A gland is a Cell (biology), cell or an Organ (biology), organ in an animal's body that produces and secretes different substances that the organism needs, either into the bloodstream or into a body cavity or outer surface. A gland may also funct ...

s regulated by the

, producing clinical effects such as increased heart rate and delayed gastric emptying. This occurs because atropine is a competitive, reversible antagonist of the muscarinic acetylcholine receptors (

being the main

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

used by the parasympathetic nervous system). Atropine is a competitive antagonist of the muscarinic acetylcholine receptor types M1, M2, M3, M4 and M5. It is classified as an anticholinergic drug ( parasympatholytic). In cardiac uses, it works as a nonselective muscarinic acetylcholinergic antagonist, increasing firing of the

sinoatrial node The sinoatrial node (also known as the sinuatrial node, SA node, sinus node or Keith–Flack node) is an ellipse, oval shaped region of special cardiac muscle in the upper back wall of the right atrium made up of Cell (biology), cells known as pa ...

(SA) and conduction through the

atrioventricular node The atrioventricular node (AV node, or Aschoff-Tawara node) electrically connects the heart's atria and ventricles to coordinate beating in the top of the heart; it is part of the electrical conduction system of the heart. The AV node lies at the ...

(AV) of the

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

, opposes the actions of the

vagus nerve The vagus nerve, also known as the tenth cranial nerve (CN X), plays a crucial role in the autonomic nervous system, which is responsible for regulating involuntary functions within the human body. This nerve carries both sensory and motor fibe ...

, blocks

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

sites, and decreases

bronchial A bronchus ( ; : bronchi, ) is a passage or airway in the lower respiratory tract that conducts Atmosphere of Earth, air into the lungs. The first or primary bronchi to branch from the trachea at the Carina of trachea, carina are the right main b ...

secretion Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mec ...

s. In the eye, atropine induces mydriasis by blocking the contraction of the circular pupillary sphincter muscle, which is normally stimulated by acetylcholine release, thereby allowing the radial iris dilator muscle to contract and dilate the pupil. Atropine induces cycloplegia by paralyzing the ciliary muscles, whose action inhibits accommodation to allow accurate refraction in children, helps to relieve pain associated with iridocyclitis, and treats ciliary block (malignant)

. The vagus (parasympathetic) nerves that innervate the heart release acetylcholine (ACh) as their primary neurotransmitter. ACh binds to muscarinic receptors (M2) that are found principally on cells comprising the sinoatrial (SA) and atrioventricular (AV) nodes. Muscarinic receptors are coupled to the G_i subunit; therefore, vagal activation decreases cAMP. Gi-protein activation also leads to the activation of KACh channels that increase potassium efflux and hyperpolarizes the cells. Increases in vagal activities to the SA node decrease the firing rate of the pacemaker cells by decreasing the slope of the pacemaker potential (phase 4 of the action potential); this decreases heart rate (negative chronotropy). The change in phase 4 slope results from alterations in potassium and calcium currents, as well as the slow-inward sodium current that is thought to be responsible for the pacemaker current (If). By hyperpolarizing the cells, vagal activation increases the cell's threshold for firing, which contributes to the reduction in the firing rate. Similar electrophysiological effects also occur at the AV node; however, in this tissue, these changes are manifested as a reduction in impulse conduction velocity through the AV node (negative dromotropy). In the resting state, there is a large degree of vagal tone in the heart, which is responsible for low resting heart rates. There is also some vagal innervation of the atrial muscle, and to a much lesser extent, the ventricular muscle. Vagus activation, therefore, results in modest reductions in atrial contractility (inotropy) and even smaller decreases in ventricular contractility. Muscarinic receptor antagonists bind to muscarinic receptors thereby preventing ACh from binding to and activating the receptor. By blocking the actions of ACh, muscarinic receptor antagonists very effectively block the effects of vagal nerve activity on the heart. By doing so, they increase heart rate and conduction velocity.

History

The name ''atropine'' was coined in the 19th century, when pure extracts from the belladonna plant '' Atropa belladonna'' were first made. The medicinal use of preparations from plants in the nightshade family is much older however. ''Mandragora'' ( mandrake) was described by

Theophrastus Theophrastus (; ; c. 371 – c. 287 BC) was an ancient Greek Philosophy, philosopher and Natural history, naturalist. A native of Eresos in Lesbos, he was Aristotle's close colleague and successor as head of the Lyceum (classical), Lyceum, the ...

in the fourth century BC for the treatment of wounds, gout, and sleeplessness, and as a love

potion A potion is a liquid "that contains medicine, poison, or something that is supposed to have magic powers." It derives from the Latin word ''potio'' which refers to a drink or the act of drinking. The term philtre is also used, often specifica ...

. By the first century AD

Dioscorides Pedanius Dioscorides (, ; 40–90 AD), "the father of pharmacognosy", was a Greek physician, pharmacologist, botanist, and author of (in the original , , both meaning "On Materia medica, Medical Material") , a 5-volume Greek encyclopedic phar ...

recognized wine of mandrake as an anaesthetic for treatment of pain or sleeplessness, to be given before surgery or cautery. The use of nightshade preparations for anesthesia, often in combination with

opium Opium (also known as poppy tears, or Lachryma papaveris) is the dried latex obtained from the seed Capsule (fruit), capsules of the opium poppy ''Papaver somniferum''. Approximately 12 percent of opium is made up of the analgesic alkaloid mor ...

, persisted throughout the Roman and Islamic Empires and continued in Europe until superseded in the 19th century by modern anesthetics. Atropine-rich extracts from the Egyptian

henbane Henbane (''Hyoscyamus niger'', also black henbane and stinking nightshade) is a poisonous plant belonging to tribe Hyoscyameae of the nightshade family ''Solanaceae''. Henbane is native to Temperate climate, temperate Europe and Siberia, and natu ...

plant (another nightshade) were used by

Cleopatra Cleopatra VII Thea Philopator (; The name Cleopatra is pronounced , or sometimes in both British and American English, see and respectively. Her name was pronounced in the Greek dialect of Egypt (see Koine Greek phonology). She was ...

in the last century B.C. to dilate the pupils of her eyes, in the hope that she would appear more alluring. Likewise, it is widely claimed that in the

Renaissance The Renaissance ( , ) is a Periodization, period of history and a European cultural movement covering the 15th and 16th centuries. It marked the transition from the Middle Ages to modernity and was characterized by an effort to revive and sur ...

, women used the juice of the berries of the nightshade '' Atropa belladonna'' to enlarge their pupils for cosmetic reasons. However, primary records of this practice are not known, and the claim may have originated much later by conflating records of actual cosmetic use (for complexion) with the mydriastic properties of atropine. A source from the late 19th century claims that the practice was also current in Paris. The pharmacological study of ''belladonna'' extracts was begun by the German

chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a graduated scientist trained in the study of chemistry, or an officially enrolled student in the field. Chemists study the composition of ...

Friedlieb Ferdinand Runge (1795–1867). In 1831, the German pharmacist Heinrich F. G. Mein (1799-1864) succeeded in preparing a pure crystalline form of the active substance, which was named ''atropine''. The substance was first synthesized by German chemist Richard Willstätter in 1901.See: * *

Natural sources

Atropine is found in many members of the family Solanaceae. The most commonly found sources are '' Atropa belladonna'' (the deadly nightshade), '' Datura innoxia'', '' D. wrightii'', '' D. metel'', and '' D. stramonium''. Other sources include members of the genera '' Brugmansia'' (angel's trumpets) and '' Hyoscyamus''.

Synthesis

Atropine can be synthesized by the reaction of tropine with tropic acid in the presence of

hydrochloric acid Hydrochloric acid, also known as muriatic acid or spirits of salt, is an aqueous solution of hydrogen chloride (HCl). It is a colorless solution with a distinctive pungency, pungent smell. It is classified as a acid strength, strong acid. It is ...

Biosynthesis

The biosynthesis of atropine starting from ''l''-phenylalanine first undergoes a

transamination Transamination is a chemical reaction that transfers an amino group to a ketoacid to form new amino acids.This pathway is responsible for the deamination of most amino acids. This is one of the major degradation pathways which convert essential a ...

forming phenylpyruvic acid which is then reduced to phenyl-lactic acid. Coenzyme A then couples phenyl-lactic acid with tropine forming littorine, which then undergoes a radical rearrangement initiated with a P450 enzyme forming hyoscyamine aldehyde. A dehydrogenase then reduces the aldehyde to a primary alcohol making (−)-hyoscyamine, which upon racemization forms atropine.

Society and culture

The species name "belladonna" ('beautiful woman' in Italian) comes from the original use of deadly nightshade to dilate the pupils of the eyes for cosmetic effect. Both atropine and the genus name for deadly nightshade derive from Atropos, one of the three Fates who, according to Greek mythology, chose how a person was to die.

Legal status

In March 2025, the Committee for Medicinal Products for Human Use of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Ryjunea, intended for slowing the progression of myopia in children aged 3 to 14 years. The applicant for this medicinal product is Santen Oy. Ryjunea was authorize for medical use in the European Union in June 2025.

References

External links

* {{Portal bar, Medicine Antidotes Chemical substances for emergency medicine Deliriants Entheogens Esters Drugs developed by Pfizer Glycine receptor agonists M1 receptor antagonists M2 receptor antagonists M3 receptor antagonists M4 receptor antagonists M5 receptor antagonists Medical mnemonics Oneirogens Ophthalmology drugs Plant toxins Secondary metabolites Tropane alkaloids Tropane alkaloids found in Solanaceae World Health Organization essential medicines Wikipedia medicine articles ready to translate