Atropine is a
tropane alkaloid
Tropane alkaloids are a class of bicyclic .2.1alkaloids and secondary metabolites that contain a tropane ring in their chemical structure. Tropane alkaloids occur naturally in many members of the plant family Solanaceae. Certain tropane alkaloi ...
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
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 t ...
, and to decrease
saliva
Saliva (commonly referred as spit or drool) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which ...
production during surgery.
It is typically given
intravenously
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
or by injection
into a muscle.
[ ]Eye drops
''Eye Drops'' is a television program on TechTV that showcased short computer animation movies and clips made using off the shelf 3D animation software. The show claimed to showcase all different types of animation, but only a very small number ...
are also available which are used to treat uveitis
Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...
and early amblyopia
Amblyopia, also called lazy eye, is a disorder of sight in which the brain fails to fully process input from one eye and over time favors the other eye. It results in decreased vision in an eye that typically appears normal in other aspects. Amb ...
. 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
Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, reduced salivary flow, or have no identifiable cause.
This symptom is very common and is o ...
, 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
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...
.[ 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
A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth de ...
, 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 bella-donna'', commonly known as deadly nightshade or belladonna, is a toxic perennial herbaceous plant in the nightshade family Solanaceae, which also includes tomatoes, potatoes and eggplant. It is native to Europe and Western Asia, ...
(''Atropa belladonna''), jimsonweed (''Datura stramonium''), mandrake
A mandrake is the root of a plant, historically derived either from plants of the genus '' Mandragora'' (in the family Solanaceae) found in the Mediterranean region, or from other species, such as '' Bryonia alba'' (the English mandrake, in the ...
(''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
The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
. It is available as a generic medication
A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
.[
]
Medical uses
Eyes
Topical
A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
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
The accommodation reflex (or ''accommodation-convergence reflex'') is a reflex action of the eye, in response to focusing on a near object, then looking at a distant object (and vice versa), comprising coordinated changes in vergence, lens shap ...
, and as a mydriatic
Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs. It may als ...
, to dilate the pupil
The pupil is a hole located in the center of the iris of the eye that allows light to strike the retina.Cassin, B. and Solomon, S. (1990) ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company. It appears black becau ...
s. Atropine degrades slowly, typically wearing off in 7 to 14 days, so it is generally used as a therapeutic mydriatic
Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs. It may als ...
, whereas tropicamide
Tropicamide, sold under the brand name Mydriacyl among others, is a medication used to dilate the pupil and help with the examination of the eye. Specifically it is used to help examine the back of the eye. It is applied as eye drops. Effect ...
(a shorter-acting cholinergic
Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word " choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation ...
antagonist) or phenylephrine
Phenylephrine, sold under the brand names Neosynephrine and Sudafed PE among others, is a medication used as a decongestant for uncomplicated nasal congestion in the form of a nasal spray or oral tablet, to dilate the pupil, to increase bloo ...
(an α-adrenergic agonist) is preferred as an aid to ophthalmic examination.
In refractive and accommodative amblyopia
Amblyopia, also called lazy eye, is a disorder of sight in which the brain fails to fully process input from one eye and over time favors the other eye. It results in decreased vision in an eye that typically appears normal in other aspects. Amb ...
, 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
Injection
Injection or injected may refer to:
Science and technology
* Injective function, a mathematical function mapping distinct arguments to distinct values
* Injection (medicine), insertion of liquid into the body with a syringe
* Injection, in broadca ...
s 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
Asystole (New Latin, from Greek privative a "not, without" + ''systolē'' "contraction") is the absence of ventricular contractions in the context of a lethal heart arrhythmia (in contrast to an induced asystole on a cooled patient on a heart-lun ...
and PEA
Pea (''pisum'' in Latin) is a pulse or fodder crop, but the word often refers to the seed or sometimes the pod of this flowering plant species. Peas are eaten as a vegetable. Carl Linnaeus gave the species the scientific name ''Pisum sativum' ...
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
Third-degree atrioventricular block (AV block) is a medical condition in which the electrical impulse generated in the sinoatrial node (SA node) in the atrium of the heart can not propagate to the ventricles.
Because the impulse is blocked, an ...
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
Third-degree atrioventricular block (AV block) is a medical condition in which the electrical impulse generated in the sinoatrial node (SA node) in the atrium of the heart can not propagate to the ventricles.
Because the impulse is blocked, an ...
with a low Purkinje or ventricular escape rhythm.
Atropine has also been used to prevent a low heart rate during intubation
Intubation (sometimes entubation) is a medical procedure involving the insertion of a tube into the body. Most commonly, intubation refers to tracheal intubation, a procedure during which an endotracheal tube is inserted into the trachea to supp ...
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
A death rattle is noisy breathing that often occurs in someone near death. Accumulation of fluids such as saliva and bronchial secretions in the throat and upper airways is the cause. Those who are dying may lose their ability to swallow and may ...
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
Organophosphate poisoning is poisoning due to organophosphates (OPs). Organophosphates are used as insecticides, medications, and nerve agents. Symptoms include increased saliva and tear production, diarrhea, vomiting, small pupils, sweating, m ...](_b ...<br></span></div> for <div class=)
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
A muscarinic acetylcholine receptor agonist, also simply known as a muscarinic agonist or as a muscarinic agent, is an agent that activates the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, lab ...
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 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 ...
s, such as tabun (GA), sarin
Sarin (NATO designation GB nerve_agent#G-series.html" ;"title="hort for nerve agent#G-series">G-series, "B" is an extremely toxic organophosphorus compound.[soman
Soman (or GD, EA 1210, Zoman, PFMP, A-255, systematic name: ''O''-pinacolyl methylphosphonofluoridate) is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibit ...]
(GD), and VX. Troops who are likely to be attacked with chemical weapon
A chemical weapon (CW) is a specialized munition that uses chemicals formulated to inflict death or harm on humans. According to the Organisation for the Prohibition of Chemical Weapons (OPCW), this can be any chemical compound intended as ...
s often carry autoinjector
An autoinjector (or auto-injector) is a medical device for injection of a premeasured dose of a particular drug. Most autoinjectors are one-use, disposable, spring-loaded syringes (prefilled syringes). By design, autoinjectors are easy to use an ...
s with atropine and oxime
In organic chemistry, an oxime is an organic compound belonging to the imines, with the general Chemical formula, formula , where R is an organic Side chain, side-chain and R' may be hydrogen, forming an aldoxime, or another organic functional g ...
, 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
Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...
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
Muscarine, L-(+)-muscarine, or muscarin is a Secondary metabolite, natural product found in certain mushrooms, particularly in ''Inocybe'' and ''Clitocybe'' species, such as the deadly ''Clitocybe dealbata, C. dealbata''. Mushrooms in the g ...
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
Irinotecan, sold under the brand name Camptosar among others, is an anti-cancer medication used to treat colon cancer and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is ...
induced acute diarrhea.
Side effects
Adverse reactions to atropine include ventricular fibrillation
Fibrillation is the rapid, irregular, and unsynchronized contraction of muscle fibers. An important occurrence is with regard to the heart.
Cardiology
There are two major classes of cardiac fibrillation: atrial fibrillation and ventricular fib ...
, supraventricular or ventricular tachycardia
Ventricular tachycardia (V-tach or VT) is a cardiovascular disorder in which fast heart rate occurs in the ventricles of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple ...
, dizziness
Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness.
Dizziness is a ...
, 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
In psychology, confusion is the quality or emotional state of being bewildered or unclear. The term "acute mental 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
Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, moo ...
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
Diphenoxylate is a centrally active opioid drug of the phenylpiperidine series that is used as a combination drug with atropine for the treatment of diarrhea. Diphenoxylate is an opioid and acts by slowing intestinal contractions; the atropine ...
or difenoxin
Difenoxin (Motofen, R-15403) is an opioid drug used, often in combination with atropine, to treat diarrhea. It is the principal metabolite of diphenoxylate.
It was first approved in the US in 1978 and in 1980 in the former West Germany.
Dife ...
, wherein the secretion-reducing effects of the atropine can also aid the antidiarrhea effects.
Although atropine treats 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 ...
(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 autoreceptor
An autoreceptor is a type of Receptor (biochemistry), receptor located in the cell membrane, membranes of neuron, nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or ...
s, 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
Physostigmine (also known as eserine from ''éséré'', the West African name for the Calabar bean) is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and ...
or pilocarpine
Pilocarpine, sold under the brand name Pilopine HS among others, is a lactone alkaloid originally extracted from plants of the Pilocarpus genus. It is used as a medication to reduce pressure inside the eye and treat dry mouth. As an eye drop ...
.
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
A muscarinic acetylcholine receptor agonist, also simply known as a muscarinic agonist or as a muscarinic agent, is an agent that activates the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, lab ...
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, also known as hyoscine, or Devil's Breath, is a medication used to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin ...
(scopolamine), 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 ...
, phenothiazine
Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history.
...
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
Benzatropine ( INN), known as benztropine in the United States and Japan, is a medication used to treat movement disorders like parkinsonism and dystonia, as well as extrapyramidal side effects of antipsychotics, including akathisia. It is ...
.
Contraindications
It is generally contraindicated
In medicine, a contraindication is a condition (a situation or factor) that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a rea ...
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
Pyloric stenosis is a narrowing of the opening from the stomach to the first part of the small intestine (the pylorus). Symptoms include projectile vomiting without the presence of bile. This most often occurs after the baby is fed. The typical a ...
, or prostatic hypertrophy, except in doses ordinarily used for preanesthesia.
Chemistry
Atropine, a tropane alkaloid
Tropane alkaloids are a class of bicyclic .2.1alkaloids and secondary metabolites that contain a tropane ring in their chemical structure. Tropane alkaloids occur naturally in many members of the plant family Solanaceae. Certain tropane alkaloi ...
, 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
Hyoscyamine (also known as daturine or duboisine) is a naturally occurring tropane alkaloid and plant toxin. It is a secondary metabolite found in certain plants of the family Solanaceae, including Hyoscyamus niger, henbane, Mandragora officina ...
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 receptor
Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...
s. 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
The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...
(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 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 ...
, 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 receptor
Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...
s (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 ...
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
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of recep ...
of the muscarinic acetylcholine receptor
Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...
types M1, M2, M3, M4 and M5. It is classified as an anticholinergic drug (parasympatholytic
A parasympatholytic agent is a substance or activity that reduces the activity of the parasympathetic nervous system.
The term parasympatholytic typically refers to the effect of a drug, although some poisons act to block the parasympathetic n ...
).
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 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 ...
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
Mydriasis is the Pupillary dilation, dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, Physical trauma, trauma, or the use of c ...
by blocking the contraction of the circular pupillary sphincter muscle, which is normally stimulated by acetylcholine release, thereby allowing the radial iris dilator muscle
The iris dilator muscle (pupil dilator muscle, pupillary dilator, radial muscle of iris, radiating fibers), is a smooth muscle of the eye, running radially in the iris and therefore fit as a dilator. The pupillary dilator consists of a spokelik ...
to contract and dilate the pupil
The pupil is a hole located in the center of the iris of the eye that allows light to strike the retina.Cassin, B. and Solomon, S. (1990) ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company. It appears black becau ...
. Atropine induces cycloplegia
Cycloplegia is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation. Because of the paralysis of the ciliary muscle, the curvature of the lens can no longer be adjusted to focus on nearby objects. This results in ...
by paralyzing the ciliary muscle
The ciliary muscle is an intrinsic muscle of the eye formed as a ring of smooth muscleSchachar, Ronald A. (2012). "Anatomy and Physiology." (Chapter 4) . in the eye's middle layer, the uvea ( vascular layer). It controls accommodation for vie ...
s, whose action inhibits accommodation to allow accurate refraction in children, helps to relieve pain associated with iridocyclitis
Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and i ...
, and treats ciliary block (malignant) 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 ...
.
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 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
''Atropa bella-donna'', commonly known as deadly nightshade or belladonna, is a toxic perennial herbaceous plant in the nightshade family Solanaceae, which also includes tomatoes, potatoes and eggplant. It is native to Europe and Western Asia, i ...
'' were first made. The medicinal use of preparations from plants in the nightshade family is much older however. ''Mandragora'' (mandrake
A mandrake is the root of a plant, historically derived either from plants of the genus '' Mandragora'' (in the family Solanaceae) found in the Mediterranean region, or from other species, such as '' Bryonia alba'' (the English mandrake, in the ...
) 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
An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia — in other words, to result in a temporary loss of sensation or awareness. They may be divided into t ...
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
The pupil is a hole located in the center of the iris of the eye that allows light to strike the retina.Cassin, B. and Solomon, S. (1990) ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company. It appears black becau ...
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
''Atropa bella-donna'', commonly known as deadly nightshade or belladonna, is a toxic perennial herbaceous plant in the nightshade family Solanaceae, which also includes tomatoes, potatoes and eggplant. It is native to Europe and Western Asia, i ...
'' 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
German(s) may refer to:
* Germany, the country of the Germans and German things
**Germania (Roman era)
* Germans, citizens of Germany, people of German ancestry, or native speakers of the German language
** For citizenship in Germany, see also Ge ...
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
Richard Martin Willstätter FRS(For) HFRSE (, 13 August 1872 – 3 August 1942) was a German organic chemist whose study of the structure of plant pigments, chlorophyll included, won him the 1915 Nobel Prize for Chemistry.
Life
Willstätter wa ...
in 1901.[See:
*
* ]
Natural sources
Atropine is found in many members of the family Solanaceae
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 ...
. The most commonly found sources are ''Atropa belladonna
''Atropa bella-donna'', commonly known as deadly nightshade or belladonna, is a toxic perennial herbaceous plant in the nightshade family Solanaceae, which also includes tomatoes, potatoes and eggplant. It is native to Europe and Western Asia, i ...
'' (the deadly nightshade
''Atropa bella-donna'', commonly known as deadly nightshade or belladonna, is a toxic perennial herbaceous plant in the nightshade family Solanaceae, which also includes tomatoes, potatoes and eggplant. It is native to Europe and Western Asia, ...
), '' Datura innoxia'', '' D. wrightii'', '' D. metel'', and '' D. stramonium''. Other sources include members of the genera ''Brugmansia
''Brugmansia'' is a genus of seven species of flowering plants in the nightshade family Solanaceae. They are woody trees or shrubs, with pendulous flowers, and have no spines on their fruit. Their large, fragrant flowers give them their common n ...
'' (angel's trumpets) and '' Hyoscyamus''.
Synthesis
Atropine can be synthesized by the reaction of tropine
Tropine is a derivative of tropane containing a hydroxyl group at the third carbon. It is also called 3-tropanol. It is a poisonous white hygroscopic crystalline powder. It is a heterocyclic alcohol and an amine.
Tropine is a central building bl ...
with tropic acid
Tropic acid is a chemical with IUPAC name 3-hydroxy-2-phenylpropanoic acid and condensed structural formula HOCH2CH PhCOOH. It is a laboratory reagent used in the chemical synthesis of atropine and hyoscyamine. Tropic acid is a chiral substance, ...
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
Phenylpyruvic acid is the organic compound with the formula C6H5CH2C(O)CO2H. It is a keto acid.
Occurrence and properties
The compound exists in equilibrium with its (''E'')- and (''Z'')-enol tautomers. It is a product from the oxidative deamin ...
which is then reduced to phenyl-lactic acid. Coenzyme A then couples phenyl-lactic acid with tropine
Tropine is a derivative of tropane containing a hydroxyl group at the third carbon. It is also called 3-tropanol. It is a poisonous white hygroscopic crystalline powder. It is a heterocyclic alcohol and an amine.
Tropine is a central building bl ...
forming littorine, which then undergoes a radical rearrangement initiated with a P450 enzyme forming hyoscyamine aldehyde.[ A ]dehydrogenase
A dehydrogenase is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN. Like all catalysts, they catalyze reverse as well as ...
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
Italian(s) may refer to:
* Anything of, from, or related to the people of Italy over the centuries
** Italians, a Romance ethnic group related to or simply a citizen of the Italian Republic or Italian Kingdom
** Italian language, a Romance languag ...
) 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
Atropos (; "without turn"), in Greek mythology, was the third of the Three Fates or Moirai, goddesses of fate and destiny. Her Roman equivalent was Morta.
Atropos was one of the Three Fates and was known as "the Inflexible One." It was Atro ...
, one of the three Fates
The Fates are a common motif in European polytheism, most frequently represented as a trio of goddesses. The Fates shape the destiny of each human, often expressed in textile metaphors such as spinning fibers into yarn, or weaving threads on a ...
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
The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...
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
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