Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of bradycardia, and to decrease saliva production during surgery.[ Eye drops are also available which are used to treat uveitis and early amblyopia.][
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Common side effects include Xerostomia, mydriasis, urinary retention, constipation, and a tachycardia.[ 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.][
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Atropine occurs naturally in a number of plants of the Solanaceae, including deadly nightshade ( Atropa belladonna), jimsonweed ( Datura stramonium), mandrake ( Mandragora officinarum)
Medical uses
Eyes
Topical atropine is used as a cycloplegic, to temporarily paralyze the accommodation reflex, and as a mydriatic, to dilate the .
In refractive and accommodative amblyopia, when occlusion is not appropriate sometimes atropine is given to induce blur in the good eye.
Antimuscarinic topical medication is effective in slowing myopia progression in children; accommodation difficulties and papillae and follicles are possible side effects.
Heart
Injections of atropine are used in the treatment of symptomatic or unstable bradycardia.
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.[* ]
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 fibers 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, 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 Drug antagonism for organophosphate poisoning by blocking the action of acetylcholine at muscarinic receptors caused by organophosphate and , such as tabun (GA), sarin (GB), soman (GD), and VX. Troops who are likely to be attacked with often carry 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, 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 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 during the Cold War.[The Battle Over Hearts and Minds
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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, blurred vision, loss of balance, dilated pupils, photophobia, dry mouth and potentially extreme confusion, deliriant , and excitation especially among the elderly. These latter effects are because atropine can cross the blood–brain barrier. Because of the hallucinogenic properties, some have used the drug recreationally, though this is potentially dangerous and often unpleasant.
In overdoses, atropine is . 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 bradycardia (slow heart rate) in emergency settings, it can cause paradoxical heart rate slowing when given at very low doses (less than 0.5 mg),[* ] One proposed mechanism for atropine's paradoxical bradycardia effect at low doses involves blockade of inhibitory presynaptic muscarinic , 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.
A common mnemonic 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), diphenhydramine, phenothiazine and benztropine.
Contraindications
It is generally contraindicated in people with glaucoma, pyloric stenosis, or prostatic hypertrophy, except in doses ordinarily used for preanesthesia.
Chemistry
Atropine, a tropane alkaloid, is an mixture of d-hyoscyamine and l-hyoscyamine,
The most common atropine compound used in medicine is atropine sulfate (monohydrate) ()2·sulfuric acid·water, 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 regulated by the parasympathetic nervous system, 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 (acetylcholine being the main neurotransmitter used by the parasympathetic nervous system).
Atropine is a competitive antagonist of the muscarinic acetylcholine receptor types M1, M2, M3, M4 and M5.
In cardiac uses, it works as a nonselective muscarinic acetylcholinergic antagonist, increasing firing of the sinoatrial node (SA) and conduction through the atrioventricular node (AV) of the heart, opposes the actions of the vagus nerve, blocks acetylcholine receptor sites, and decreases bronchial .
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 , whose action inhibits accommodation to allow accurate refraction in children, helps to relieve pain associated with iridocyclitis, 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 the Gi subunit; therefore, vagal activation decreases cAMP. Gi-protein activation also leads to the activation of 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.[ Goodman and Gilman's Pharmacological Basis of Therapeutics, q.v. "Muscarinic receptor antagonists - History", p. 163 of the 2001 edition.] The medicinal use of preparations from Solanaceae is much older however. Mandragora (mandrake) was described by Theophrastus in the fourth century BC for the treatment of wounds, gout, and sleeplessness, and as a love potion. By the first century AD Dioscorides recognized wine of mandrake as an anaesthetic for treatment of pain or sleeplessness, to be given before surgery or cautery.
Atropine-rich extracts from the Egyptian henbane plant (another nightshade) were used by Cleopatra 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, 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
The pharmacological study of belladonna extracts was begun by the Germany chemist Friedlieb Ferdinand Runge (1795–1867). In 1831, the German pharmacist Heinrich F. G. Mein (1799-1864)[Atropine was also independently isolated in 1833 by Geiger and Hesse:
] The substance was first synthesized by German chemist Richard Willstätter in 1901.[See:
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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, Datura wrightii, Datura 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.
Biosynthesis
The biosynthesis of atropine starting from Phenylalanine first undergoes a transamination forming phenylpyruvic acid which is then reduced to phenyl-lactic acid.[ A dehydrogenase then reduces the aldehyde to a primary alcohol making (−)-hyoscyamine, which upon racemization forms atropine.][
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Society and culture
The species name "belladonna" ('beautiful woman' in Italian language) 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 Moirai 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 (CHMP) of the European 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.[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.] Ryjunea was authorized for medical use in the European Union in June 2025.
In March 2025, the CHMP recommended the refusal of a pediatric use marketing authorization for Atropine sulfate FGK, a medicine intended for the treatment of myopia (short-sightedness) in children aged 6 to 10 years of age.[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.] In June 2025, FGK Representative Service requested a re-examination by the CHMP.
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