Atropine is atropane alkaloid andanticholinergic medication used to treat certain types ofnerve agent andpesticide poisonings as well as some types ofslow heart rate, and to decreasesaliva production during surgery.^[6] It is typically givenintravenously or by injectioninto a muscle.^[6]Eye drops are also available which are used to treatuveitis and earlyamblyopia.^[7][8] The intravenous solution usually begins working within a minute and lasts half an hour to an hour.^[5] Large doses may be required to treat some poisonings.^[6]

Atropine

Clinical data
Trade names	Atropen, others
Other names	Daturin[1]
AHFS/Drugs.com	Monograph
MedlinePlus	a682487
License data	US DailyMed: Atropine
Pregnancy category	AU: A
Routes of administration	By mouth,intravenous,intramuscular,rectal,ophthalmic
Drug class	antimuscarinic (anticholinergic)
ATC code	A03BA01 (WHO)S01FA01 (WHO)
Legal status
Legal status	AU:S4 (Prescription only)[2] US:℞-only[3][4]
Pharmacokinetic data
Bioavailability	25%
Metabolism	≥50%hydrolysed totropine andtropic acid
Onset of action	c. 1 minute[5]
Eliminationhalf-life	2 hours
Duration of action	30 to 60 min[5]
Excretion	15–50% excreted unchanged in urine
Identifiers
IUPAC name (RS)-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl) 3-hydroxy-2-phenylpropanoate
CAS Number	51-55-8 Y
PubChemCID	174174
IUPHAR/BPS	320
DrugBank	DB00572 Y
ChemSpider	10194105 Y
UNII	7C0697DR9I
KEGG	D00113 Y
ChEBI	CHEBI:16684 Y
ChEMBL	ChEMBL517712
ECHA InfoCard	100.000.096
Chemical and physical data
Formula	C17H23NO3
Molar mass	289.375 g·mol−1
3D model (JSmol)	Interactive image
SMILES CN3[C@H]1CC[C@@H]3C[C@@H](C1)OC(=O)C(CO)c2ccccc2
InChI InChI=1S/C17H23NO3/c1-18-13-7-8-14(18)10-15(9-13)21-17(20)16(11-19)12-5-3-2-4-6-12/h2-6,13-16,19H,7-11H2,1H3/t13-,14+,15+,16? Y Key:RKUNBYITZUJHSG-SPUOUPEWSA-N Y
NY (what is this?)  (verify)

Commonside effects includedry mouth,abnormally large pupils,urinary retention,constipation, and afast heart rate.^[6] It should generally not be used in people withclosed-angle glaucoma.^[6] While there is no evidence that its use during pregnancy causesbirth defects, this has not been well studied so sound clinical judgment should be used.^[9] It is likely safe during breastfeeding.^[9] It is anantimuscarinic (a type of anticholinergic) that works by inhibiting theparasympathetic nervous system.^[6]

Atropine occurs naturally in a number of plants of thenightshade family, includingdeadly nightshade (Atropa belladonna),jimsonweed (Datura stramonium),mandrake (Mandragora officinarum)^[10] andangel's trumpet (Brugmansia).^[11] Atropine was first isolated in 1833.^[12] It is on theWorld Health Organization's List of Essential Medicines.^[13] It is available as ageneric medication.^[6][14][15]

Topical atropine is used as acycloplegic, to temporarily paralyze theaccommodation reflex, and as amydriatic, to dilate thepupils.^[16] Atropine degrades slowly, typically wearing off in 7 to 14 days, so it is generally used as a therapeuticmydriatic, whereastropicamide (a shorter-actingcholinergic antagonist) orphenylephrine (an α-adrenergic agonist) is preferred as an aid toophthalmic examination.^[16]

In refractive and accommodativeamblyopia, when occlusion is not appropriate sometimes atropine is given to induce blur in the good eye.^[17] Evidence suggests that atropine penalization is just as effective as occlusion in improving visual acuity.^[18][19]

Antimuscarinic topical medication is effective in slowing myopia progression in children; accommodation difficulties and papillae and follicles are possible side effects.^[20] All doses of atropine appear similarly effective, while higher doses have greater side effects.^[21] 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.^[21][22]

Injections of atropine are used in the treatment of symptomatic or unstablebradycardia.

Atropine was previously included in international resuscitation guidelines for use in cardiac arrest associated withasystole andPEA but was removed from these guidelines in 2010 due to a lack of evidence for its effectiveness.^[23] 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).^[24]

Atropine is also useful in treatingsecond-degree heart block Mobitz type 1 (Wenckebach block), and alsothird-degree heart block with a highPurkinje orAV-nodalescape rhythm. It is usually not effective insecond-degree heart block Mobitz type 2, and inthird-degree heart block with a low Purkinje or ventricular escape rhythm.^{[citation needed]}

Atropine has also been used to prevent a low heart rate duringintubation of children; however, the evidence does not support this use.^[25]

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 treatinghyperhidrosis, and can prevent thedeath 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.^[26]

Atropine acts as anantagonist fororganophosphate poisoning by blocking the action ofacetylcholine atmuscarinic receptors caused byorganophosphateinsecticides andnerve agents, such astabun (GA),sarin (GB),soman (GD), andVX. Troops who are likely to be attacked withchemical weapons often carryautoinjectors with atropine andoxime, 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 oximepralidoxime chloride.

Some of the nerve agents attack and destroyacetylcholinesterase byphosphorylation, 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 ordiphenhydramine can be used to treatmuscarine intoxication.^{[medical citation needed]}

Atropine was added to cafeteria salt shakers in an attempt to poison the staff ofRadio Free Europe during theCold War.^[27][28]

Atropine has been observed to prevent or treatirinotecan induced acute diarrhea.^[29]

Adverse reactions to atropine include ventricularfibrillation, supraventricular orventricular tachycardia,dizziness,nausea, blurred vision, loss of balance, dilated pupils,photophobia, dry mouth and potentially extremeconfusion, delirianthallucinations, andexcitation especially among the elderly. These latter effects are because atropine can cross theblood–brain barrier. Because of thehallucinogenic properties, some have used the drugrecreationally, though this is potentially dangerous and often unpleasant.^{[medical citation needed]}

In overdoses, atropine ispoisonous.^{[medical citation needed]} Atropine is sometimes added to potentially addictive drugs, particularly antidiarrhea opioid drugs such asdiphenoxylate ordifenoxin, wherein the secretion-reducing effects of the atropine can also aid the antidiarrhea effects.^{[medical citation needed]}

Although atropine treatsbradycardia (slow heart rate) in emergency settings, it can cause paradoxical heart rate slowing when given at very low doses (i.e. <0.5 mg),^[30] presumably as a result of central action in the CNS.^[31] One proposed mechanism for atropine's paradoxical bradycardia effect at low doses involves blockade of inhibitory presynaptic muscarinicautoreceptors, thereby blocking a system that inhibits the parasympathetic response.^[32]

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.^[33]The antidote to atropine isphysostigmine orpilocarpine.^{[medical citation needed]}

A commonmnemonic 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".^[34] These associations reflect the specific changes of warm, dry skin from decreased sweating, blurry vision, decreased lacrimation, vasodilation, and central nervous system effects onmuscarinic receptors, type 4 and 5. This set of symptoms is known asanticholinergic toxidrome, and may also be caused by other drugs with anticholinergic effects, such ashyoscine hydrobromide (scopolamine),diphenhydramine,phenothiazineantipsychotics andbenztropine.^[35]

It is generallycontraindicated in people withglaucoma,pyloric stenosis, orprostatic hypertrophy, except in doses ordinarily used for preanesthesia.^[3]

Atropine, atropane alkaloid, is anenantiomeric mixture ofd-hyoscyamine andl-hyoscyamine,^[36] with most of its physiological effects due tol-hyoscyamine, the 3(S)-endo isomer of atropine. Its pharmacological effects are due to binding tomuscarinic 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.^[37] Effects on the iris and ciliary muscle may persist for longer than 72 hours.

The most common atropine compound used in medicine is atropinesulfate (monohydrate) (C
₁₇H
₂₃NO
₃)₂·H₂SO₄·H₂O, the full chemical name is 1α H, 5α H-Tropan-3-α ol (±)-tropate(ester), sulfate monohydrate.

In general, atropine counters the "rest and digest" activity ofglands regulated by theparasympathetic nervous system, producing clinical effects such as increased heart rate and delayed gastric emptying. This occurs because atropine is a competitive, reversible antagonist of themuscarinic acetylcholine receptors (acetylcholine being the mainneurotransmitter used by the parasympathetic nervous system).

Atropine is acompetitive antagonist of themuscarinic acetylcholine receptor typesM1,M2,M3,M4 andM5.^[38] It is classified as ananticholinergic drug (parasympatholytic).

In cardiac uses, it works as a nonselective muscarinic acetylcholinergic antagonist, increasing firing of thesinoatrial node (SA) and conduction through theatrioventricular node (AV) of theheart, opposes the actions of thevagus nerve, blocksacetylcholinereceptor sites, and decreasesbronchialsecretions.

In the eye, atropine inducesmydriasis by blocking the contraction of the circularpupillary sphincter muscle, which is normally stimulated by acetylcholine release, thereby allowing the radialiris dilator muscle to contract and dilate thepupil. Atropine inducescycloplegia by paralyzing theciliary muscles, whose action inhibits accommodation to allow accurate refraction in children, helps to relieve pain associated withiridocyclitis, and treats ciliary block (malignant)glaucoma.

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 theG_i subunit; therefore, vagal activation decreases cAMP. Gi-protein activation also leads to the activation ofKACh 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.

The nameatropine was coined in the 19th century, when pure extracts from the belladonna plantAtropa belladonna were first made.^[39] The medicinal use of preparations fromplants in the nightshade family is much older however.Mandragora (mandrake) was described byTheophrastus in the fourth century B.C. for the treatment of wounds, gout, and sleeplessness, and as a lovepotion. By the first century A.D.Dioscorides recognized wine of mandrake as ananaesthetic for treatment of pain or sleeplessness, to be given before surgery or cautery.^[34] The use of nightshade preparations for anesthesia, often in combination withopium, persisted throughout the Roman and Islamic Empires and continued in Europe until superseded in the 19th century by modern anesthetics.^{[citation needed]}

Atropine-rich extracts from the Egyptianhenbane plant (another nightshade) were used byCleopatra in the last century B.C. to dilate thepupils of her eyes, in the hope that she would appear more alluring. Likewise in theRenaissance, women used the juice of the berries of the nightshadeAtropa belladonna to enlarge their pupils for cosmetic reasons. This practice resumed briefly in the late nineteenth and early twentieth century in Paris.^{[citation needed]}

The pharmacological study ofbelladonna extracts was begun by theGermanchemistFriedlieb Ferdinand Runge (1795–1867). In 1831, the German pharmacist Heinrich F. G. Mein (1799-1864)^[40] succeeded in preparing a pure crystalline form of the active substance, which was namedatropine.^[41][42] The substance was first synthesized by German chemistRichard Willstätter in 1901.^[43]

Atropine is found in many members of the familySolanaceae. The most commonly found sources areAtropa belladonna (thedeadly nightshade),Datura innoxia,D. wrightii,D. metel, andD. stramonium. Other sources include members of the generaBrugmansia (angel's trumpets) andHyoscyamus.^[36]

Atropine can be synthesized by the reaction oftropine withtropic acid in the presence ofhydrochloric acid.

The biosynthesis of atropine starting froml-phenylalanine first undergoes atransamination formingphenylpyruvic acid which is then reduced to phenyl-lactic acid.^[44] Coenzyme A then couples phenyl-lactic acid withtropine forminglittorine, which then undergoes a radical rearrangement initiated with aP450 enzyme forming hyoscyamine aldehyde.^[44] Adehydrogenase then reduces the aldehyde to a primary alcohol making (−)-hyoscyamine, which upon racemization forms atropine.^[44]

The species name "belladonna" ('beautiful woman' inItalian) 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 fromAtropos, one of the threeFates who, according to Greek mythology, chose how a person was to die.^[34]

In March 2025, theCommittee for Medicinal Products for Human Use of theEuropean Medicines Agency 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.^[45] The applicant for this medicinal product is Santen Oy.^[45]

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