Atropine

Atropine

Overview
Atropine is a naturally occurring tropane alkaloid
Tropane alkaloid
Tropane alkaloids are a class of alkaloids and secondary metabolites that contain a tropane ring in their chemical structure...

 extracted from deadly nightshade
Deadly nightshade
Atropa belladonna or Atropa bella-donna, commonly known as Belladonna, Devil's Berries, Death Cherries or Deadly Nightshade, is a perennial herbaceous plant in the family Solanaceae, native to Europe, North Africa, and Western Asia. The foliage and berries are extremely toxic, containing tropane...

 (Atropa belladonna), Jimson weed
Datura stramonium
Datura stramonium, known by the common names Jimson weed, devil's trumpet, devil's weed, thorn apple, tolguacha, Jamestown weed, stinkweed, locoweed, datura, pricklyburr, devil's cucumber, Hell's Bells, moonflower and, in South Africa, malpitte and mad seeds, is a common weed in the...

 (Datura stramonium), mandrake
Mandrake (plant)
Mandrake is the common name for members of the plant genus Mandragora, particularly the species Mandragora officinarum, belonging to the nightshades family...

 (Mandragora officinarum) and other plants of the family Solanaceae
Solanaceae
Solanaceae are a family of flowering plants that include a number of important agricultural crops as well as many toxic plants. The name of the family comes from the Latin Solanum "the nightshade plant", but the further etymology of that word is unclear...

. It is a secondary metabolite
Secondary metabolite
Secondary metabolites are organic compounds that are not directly involved in the normal growth, development, or reproduction of an organism. Unlike primary metabolites, absence of secondary metabolities does not result in immediate death, but rather in long-term impairment of the organism's...

 of these plants and serves as a drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

 with a wide variety of effects. It is a competitive antagonist
Competitive antagonist
A competitive antagonist is a receptor antagonist that binds to a receptor but does not activate the receptor. The antagonist will compete with available agonist for receptor binding sites on the same receptor...

 for the muscarinic acetylcholine receptor
Muscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...

. It is classified as an anticholinergic drug (parasympatholytic
Parasympatholytic
A parasympatholytic agent is a substance or activity that reduces the activity of the parasympathetic nervous system. A parasympatholytic agent is a substance or activity that reduces the activity of the parasympathetic nervous system. A parasympatholytic agent is a substance or activity that...

). The species name "belladonna" comes from the original use of deadly nightshade as a way of dilating women's pupils to make them beautiful.
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Encyclopedia
Atropine is a naturally occurring tropane alkaloid
Tropane alkaloid
Tropane alkaloids are a class of alkaloids and secondary metabolites that contain a tropane ring in their chemical structure...

 extracted from deadly nightshade
Deadly nightshade
Atropa belladonna or Atropa bella-donna, commonly known as Belladonna, Devil's Berries, Death Cherries or Deadly Nightshade, is a perennial herbaceous plant in the family Solanaceae, native to Europe, North Africa, and Western Asia. The foliage and berries are extremely toxic, containing tropane...

 (Atropa belladonna), Jimson weed
Datura stramonium
Datura stramonium, known by the common names Jimson weed, devil's trumpet, devil's weed, thorn apple, tolguacha, Jamestown weed, stinkweed, locoweed, datura, pricklyburr, devil's cucumber, Hell's Bells, moonflower and, in South Africa, malpitte and mad seeds, is a common weed in the...

 (Datura stramonium), mandrake
Mandrake (plant)
Mandrake is the common name for members of the plant genus Mandragora, particularly the species Mandragora officinarum, belonging to the nightshades family...

 (Mandragora officinarum) and other plants of the family Solanaceae
Solanaceae
Solanaceae are a family of flowering plants that include a number of important agricultural crops as well as many toxic plants. The name of the family comes from the Latin Solanum "the nightshade plant", but the further etymology of that word is unclear...

. It is a secondary metabolite
Secondary metabolite
Secondary metabolites are organic compounds that are not directly involved in the normal growth, development, or reproduction of an organism. Unlike primary metabolites, absence of secondary metabolities does not result in immediate death, but rather in long-term impairment of the organism's...

 of these plants and serves as a drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

 with a wide variety of effects. It is a competitive antagonist
Competitive antagonist
A competitive antagonist is a receptor antagonist that binds to a receptor but does not activate the receptor. The antagonist will compete with available agonist for receptor binding sites on the same receptor...

 for the muscarinic acetylcholine receptor
Muscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...

. It is classified as an anticholinergic drug (parasympatholytic
Parasympatholytic
A parasympatholytic agent is a substance or activity that reduces the activity of the parasympathetic nervous system. A parasympatholytic agent is a substance or activity that reduces the activity of the parasympathetic nervous system. A parasympatholytic agent is a substance or activity that...

). The species name "belladonna" comes from the original use of deadly nightshade as a way of dilating women's pupils to make them beautiful. Both atropine and the genus name for deadly nightshade derive from Atropos
Atropos
Atropos or Aisa , in Greek mythology, was one of the three Moirae, goddesses of fate and destiny. Her Roman equivalent was Morta.Atropos or Aisa was the oldest of the Three Fates, and was known as the "inflexible" or "inevitable." It was Atropos who chose the mechanism of death and ended the life...

, one of the three Fates
Moirae
The Moirae, Moerae or Moirai , in Greek mythology, were the white-robed incarnations of destiny . Their number became fixed at three...

 who, according to Greek mythology, chose how a person was to die. Atropine is a core medicine in the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

's "Essential Drugs List", which is a list of minimum medical needs for a basic health care system.

Physiological effects and uses


Atropine increases firing of the sinoatrial node
Sinoatrial node
The sinoatrial node is the impulse-generating tissue located in the right atrium of the heart, and thus the generator of normal sinus rhythm. It is a group of cells positioned on the wall of the right atrium, near the entrance of the superior vena cava...

 (SA) and conduction through the atrioventricular node
Atrioventricular node
The atrioventricular node is a part of the electrical control system of the heart that coordinates heart rate. It electrically connects atrial and ventricular chambers...

 (AV) of the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

, opposes the actions of the vagus nerve
Vagus nerve
The vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves...

, blocks acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

 sites, and decreases bronchial secretion
Secretion
Secretion is the process of elaborating, releasing, and oozing chemicals, or a secreted chemical substance from a cell or gland. In contrast to excretion, the substance may have a certain function, rather than being a waste product...

s.

In general, atropine lowers the parasympathetic activity of all muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...

s and gland
Gland
A gland is an organ in an animal's body that synthesizes a substance for release of substances such as hormones or breast milk, often into the bloodstream or into cavities inside the body or its outer surface .- Types :...

s regulated by the parasympathetic nervous system
Parasympathetic nervous system
The parasympathetic nervous system is one of the two main divisions of the autonomic nervous system . The ANS is responsible for regulation of internal organs and glands, which occurs unconsciously...

. This occurs because atropine is a competitive antagonist
Competitive antagonist
A competitive antagonist is a receptor antagonist that binds to a receptor but does not activate the receptor. The antagonist will compete with available agonist for receptor binding sites on the same receptor...

 of the muscarinic acetylcholine receptor
Acetylcholine receptor
An acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.-Classification:...

s (acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 being the main neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 used by the parasympathetic nervous system). Therefore, it may cause swallowing difficulties and reduced secretions.

Ophthalmic use


Topical
Topical
In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, anus, throat, eyes and ears.Many topical medications are epicutaneous, meaning that they are applied directly to the skin...

 atropine is used as a cycloplegic, to temporarily paralyze the accommodation reflex
Accommodation reflex
The accommodation reflex is a reflex action of the eye, in response to focusing on a near object, then looking at distant object , comprising coordinated changes in vergence, lens shape and pupil size...

, and as a mydriatic, to dilate the pupil
Pupil
The pupil is a hole located in the center of the iris of the eye that allows light to enter the retina. It appears black because most of the light entering the pupil is absorbed by the tissues inside the eye. In humans the pupil is round, but other species, such as some cats, have slit pupils. In...

s. Atropine degrades slowly, typically wearing off in 7 to 14 days, so it is generally used as a therapeutic mydriatic, whereas tropicamide
Tropicamide
Tropicamide is an anticholinergic used as a mydriatic. In Russia, it is used to some degree as an inexpensive recreational drug...

 (a shorter-acting cholinergic
Cholinergic
The word choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin...

 antagonist) or phenylephrine
Phenylephrine
Phenylephrine is a selective α1-adrenergic receptor agonist used primarily as a decongestant, as an agent to dilate the pupil, and to increase blood pressure...

 (an α-adrenergic agonist) is preferred as an aid to ophthalmic
Ophthalmology
Ophthalmology is the branch of medicine that deals with the anatomy, physiology and diseases of the eye. An ophthalmologist is a specialist in medical and surgical eye problems...

 examination. Atropine induces mydriasis
Mydriasis
Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...

 by blocking contraction of the circular pupillary sphincter muscle, which is normally stimulated by acetylcholine release, thereby allowing the radial pupillary dilator muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...

 to contract and dilate the pupil
Pupil
The pupil is a hole located in the center of the iris of the eye that allows light to enter the retina. It appears black because most of the light entering the pupil is absorbed by the tissues inside the eye. In humans the pupil is round, but other species, such as some cats, have slit pupils. In...

. Atropine induces cycloplegia
Cycloplegia
Cycloplegia is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation.-Anatomy:The iris is the heavily pigmented colored part of the eye. It has a contractile diaphragm in front of the lens with a central opening called the pupil...

 by paralyzing the ciliary muscle
Ciliary muscle
The ciliary muscle is a ring of striated smooth muscle in the eye's middle layer that controls accommodation for viewing objects at varying distances and regulates the flow of aqueous humour into Schlemm's canal. It changes the shape of the lens within the eye not the size of the pupil which is...

s, whose action inhibits accommodation to allow accurate refraction in children, helps to relieve pain associated with iridocyclitis
Iridocyclitis
Iridocyclitis, a type of anterior uveitis, is a condition in which the uvea of the eye is inflamed.Iridocyclitis isInflammation of the iris and the ciliary body.- Symptoms :Symptoms include:* Photophobia* Redness* Watering of the eyes* Lacrimation...

, and treats ciliary block (malignant) glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

. Atropine is contraindicated in patients pre-disposed to narrow angle glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

.

Atropine can be given to patients who have direct globe trauma.

Resuscitation


Injection
Injection (medicine)
An injection is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body...

s of atropine are used in the treatment of bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...

 (an extremely low heart rate). Atropine blocks the action of the vagus nerve
Vagus nerve
The vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves...

, a part of the parasympathetic system of the heart whose main action is to decrease heart rate. Therefore, its primary function in this circumstance is to increase the heart rate. Atropine was previously included in international resuscitation guidelines for use in cardiac arrest associated with asystole
Asystole
In medicine, asystole is a state of no cardiac electrical activity, hence no contractions of the myocardium and no cardiac output or blood flow...

 and PEA
Pulseless electrical activity
Pulseless electrical activity or PEA refers a cardiac arrest situation in which a heart rhythm is observed on the electrocardiogram that should be producing a pulse, but is not...

, but was removed from these guidelines in 2010 due to a lack of evidence. For symptomatic bradycardia, the usual dosage is 0.5 to 1 mg IV push, may repeat every 3 to 5 minutes up to a maximum dose of 3 mg.

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
Purkinje fibers
For the nervous cells, see Purkinje cellPurkinje fibers are located in the inner ventricular walls of the heart, just beneath the endocardium...

 or AV-nodal
Atrioventricular node
The atrioventricular node is a part of the electrical control system of the heart that coordinates heart rate. It electrically connects atrial and ventricular chambers...

 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 is contraindicated in ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...

-induced conduction block, because the drug increases oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

 demand of the AV nodal tissue, thereby aggravating ischemia and the resulting heart block
Heart block
A heart block can be a blockage at any level of the electrical conduction system of the heart .* Blocks that occur within the sinoatrial node are described as SA nodal blocks....

.

One of the main actions of the parasympathetic nervous system
Parasympathetic nervous system
The parasympathetic nervous system is one of the two main divisions of the autonomic nervous system . The ANS is responsible for regulation of internal organs and glands, which occurs unconsciously...

 is to stimulate the M2 muscarinic receptor
Muscarinic acetylcholine receptor M2
The muscarinic acetylcholine receptor M2, also known as the cholinergic receptor, muscarinic 2, is a muscarinic acetylcholine receptor.-Heart:...

 in the heart, but atropine inhibits this action.

Secretions and bronchoconstriction


Atropine's actions on the parasympathetic nervous system inhibits salivary and mucus glands. The drug may also inhibit sweating via the sympathetic nervous system. This can be useful in treating hyperhidrosis
Hyperhidrosis
Hyperhidrosis is the condition characterized by abnormally increased perspiration, in excess of that required for regulation of body temperature.-Classification:Hyperhidrosis can either be generalized or localized to specific parts of the body...

, and can prevent the death rattle
Death rattle
A death rattle is a medical term that describes the sound produced by someone who is near death when saliva accumulates in the throat. Those who are dying may lose their ability to swallow, resulting in such an accumulation...

 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.

Treatment for organophosphate poisoning


Atropine is not an actual antidote for organophosphate poisoning. However, by blocking the action of acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 at muscarinic receptors, atropine also serves as a treatment for poisoning by organophosphate
Organophosphate
An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...

 insecticide
Insecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...

s and nerve gases, such as tabun
Tabun (nerve agent)
Tabun or GA is an extremely toxic chemical substance. It is a clear, colorless, and tasteless liquid with a faint fruity odor. It is classified as a nerve agent because it fatally interferes with normal functioning of the mammalian nervous system...

 (GA), sarin
Sarin
Sarin, or GB, is an organophosphorus compound with the formula [2CHO]CH3PF. It is a colorless, odorless liquid, which is used as a chemical weapon. It has been classified as a weapon of mass destruction in UN Resolution 687...

 (GB), soman
Soman
Soman, or GD , is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibiting the cholinesterase enzyme. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations according to UN...

 (GD) and VX
VX (nerve agent)
VX, IUPAC name O-ethyl S-[2-ethyl] methylphosphonothioate, is an extremely toxic substance whose only application is in chemical warfare as a nerve agent. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations in UN Resolution 687...

. Troops who are likely to be attacked with chemical weapons often carry autoinjector
Autoinjector
An autoinjector is a medical device designed to deliver a single dose of a particular drug....

s with atropine and obidoxime
Obidoxime
Obidoxime is a member of the oxime family used to treat nerve gas poisoning. Oximes are drugs known for their ability to reverse the binding of organophosphorus compounds to the enzyme acetylcholinesterase ....

, which can be quickly injected into the thigh
Great saphenous vein
The great saphenous vein , also long saphenous vein, is the large superficial vein of the leg and thigh.The terms "safaina" and "el safin" have both been claimed as the origin for the word "saphenous."-Path:The GSV originates from where the dorsal vein of the first digit...

. Atropine is often used in conjunction with pralidoxime chloride.

Atropine is given as a treatment for SLUDGE (salivation, lacrimation, urination
Urination
Urination, also known as micturition, voiding, peeing, weeing, pissing, and more rarely, emiction, is the ejection of urine from the urinary bladder through the urethra to the outside of the body. In healthy humans the process of urination is under voluntary control...

, diaphoresis
Diaphoresis
Diaphoresis is excessive sweating commonly associated with shock and other medical emergency conditions.Diaphoretic is the state of perspiring profusely, or something that has the power to cause increased perspiration....

, gastrointestinal motility, emesis) symptoms caused by organophosphate poisoning. Another mnemonic is DUMBBELSS, which stands for diarrhea, urination, miosis, bradycardia, bronchoconstriction, excitation (as of muscle in the form of fasciculations and CNS), lacrimation, salivation, and sweating (only sympathetic innervation using Musc receptors).

Some of the nerve agents attack and destroy acetylcholinesterase
Acetylcholinesterase
"Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...

 by phosphorylation, so the action of acetylcholine becomes prolonged, pralidoxime (2-PAM) is the cure for organophosphate poisoning because it can 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.

Optical penalisation


In refractive and accommodative amblyopia
Amblyopia
Amblyopia, also known as lazy eye, is a disorder of the visual system that is characterized by a vision deficiency in an eye that is otherwise physically normal, or out of proportion to associated structural abnormalities of the eye...

, when occlusion is not appropriate sometimes atropine is given to induce blur in the good eye.

Side-effects and overdose


Adverse reactions to atropine include ventricular fibrillation
Fibrillation
Fibrillation is the rapid, irregular, and unsynchronized contraction of muscle fibers. An important occurrence is with regards to the heart.-Cardiology:There are two major classes of cardiac fibrillation: atrial fibrillation and ventricular fibrillation....

, supraventricular or ventricular tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

, dizziness
Vertigo (medical)
Vertigo is a type of dizziness, where there is a feeling of motion when one is stationary. The symptoms are due to a dysfunction of the vestibular system in the inner ear...

, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

, blurred vision, loss of balance, dilated pupils, photophobia
Photophobia
Photophobia is a 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 of actual physical photosensitivity of the eyes, though the term...

, dry mouth and potentially extreme confusion
ConFusion
ConFusion is an annual science fiction convention organized by the Stilyagi Air Corps and its parent organization, the Ann Arbor Science Fiction Association. Commonly, it is held the third weekend of January. It is the oldest science fiction convention in Michigan, a regional, general SF con...

, dissociative hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

s and excitation
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...

 especially amongst the elderly. These latter effects are because atropine is able to cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

. Because of the hallucinogenic
Psychedelics, dissociatives and deliriants
This general group of pharmacological agents can be divided into three broad categories: psychedelics, dissociatives, and deliriants. These classes of psychoactive drugs have in common that they can cause subjective changes in perception, thought, emotion and consciousness...

 properties, some have used the drug recreationally, though this is potentially dangerous and often unpleasant.

In overdoses, atropine is poison
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....

ous. Atropine is sometimes added to potentially addictive drugs, particularly anti-diarrhea opioid drugs such as diphenoxylate
Diphenoxylate
Diphenoxylate is an opioid agonist used for the treatment of diarrhea that acts by slowing intestinal contractions and peristalsis allowing the body to consolidate intestinal contents and prolong transit time, thus allowing the intestines to draw moisture out of them at a normal or higher rate and...

 or difenoxin
Difenoxin
Difenoxin is a 4-phenylpiperidine derivative that is related to the opioid analgesic drug pethidine and more distantly related to alphaprodine and piritramide, and it is an active metabolite of the anti-diarrhoea drug diphenoxylate. Difenoxin et al...

, wherein the secretion-reducing effects of the atropine can also aid the anti-diarrhea effects.

Although atropine treats bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...

 (slow heart rate) in emergency settings, it can cause paradoxical heart rate slowing when given at very low doses, presumably as a result of central action in the CNS.

Atropine is incapacitating at doses of 10 to 20 mg per person. Its LD50 is estimated to be 453 mg per person (per oral) with a probit slope of 1.8.
The antidote to atropine is physostigmine
Physostigmine
Physostigmine is a parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean....

 or pilocarpine
Pilocarpine
Pilocarpine is a parasympathomimetic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its...

.

A common mnemonic
Mnemonic
A mnemonic , or mnemonic device, is any learning technique that aids memory. To improve long term memory, mnemonic systems are used to make memorization easier. Commonly encountered mnemonics are often verbal, such as a very short poem or a special word used to help a person remember something,...

 used to describe the physiologic manifestations of atropine overdose is: as per Jon Blinkey "hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter". These associations reflect the specific changes of warm, dry skin from decreased sweating, blurry vision, decreased sweating/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 diphenhydramine
Diphenhydramine
Diphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason...

, phenothiazine
Phenothiazine
Phenothiazine is an organic compound that occurs in various antipsychotic and antihistaminic drugs. It has the formula S2NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related to the thiazine-class of heterocyclic compounds...

 antipsychotic
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...

s and benztropine
Benztropine
Benzatropine , also known as benztropine , is an anticholinergic marketed under the trade name Cogentin which is used in the treatment of Parkinson's disease, parkinsonism, akathisia, and dystonia.- Indications :...

.

Chemistry and pharmacology


Atropine is a racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...

 mixture of d
Levorotation and dextrorotation
Dextrorotation and levorotation refer, respectively, to the properties of rotating plane polarized light clockwise or counterclockwise , seen by an observer whom the light is approaching...

-hyoscyamine
Hyoscyamine
Hyoscyamine is a tropane alkaloid. It is a secondary metabolite found in certain plants of the Solanaceae family, including henbane , mandrake , jimsonweed , tomato and deadly nightshade...

 and l-hyoscyamine, with most of its physiological effects due to l-hyoscyamine. Its pharmacological effects are due to binding to muscarinic acetylcholine receptor
Acetylcholine receptor
An acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.-Classification:...

s. It is an antimuscarinic agent. Significant levels are achieved in the CNS within 30 minutes to 1 hour and disappears rapidly from the blood with a half-life of 2 hours. About 60% is excreted unchanged in the urine, most of the rest appears in urine as hydrolysis and conjugation products. 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
Sulfate
In inorganic chemistry, a sulfate is a salt of sulfuric acid.-Chemical properties:...

 (C
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...

17H
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...

23N
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...

O
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

3)2·H2SO4
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...

·H2O
Water
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...

, the full chemical name is 1α H, 5α H-Tropan-3-α ol (±)-tropate(ester), sulfate monohydrate.

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-protein; 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 activity to the SA node decreases 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 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 on 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


Mandragora
Mandrágora
For other uses see Mandragora .La Mandrágora was a Chilean Surrealist group "officially founded" on 12 July 1938 by Braulio Arenas , Teófilo Cid and Enrique Gómez Correa . The group had met in Talca and first started exchanging in 1932...

(mandrake) was described by Theophrastus
Theophrastus
Theophrastus , a Greek native of Eresos in Lesbos, was the successor to Aristotle in the Peripatetic school. He came to Athens at a young age, and initially studied in Plato's school. After Plato's death he attached himself to Aristotle. Aristotle bequeathed to Theophrastus his writings, and...

 in the fourth century B.C. for treatment of wounds, gout, and sleeplessness, and as a love potion
Love potion
Love potion may refer to:* In folklore, mythology, or works of fiction, a love potion may refer to a type of potion designed to create feelings of love towards a person* Lappish Hag's Love Potion, an alcoholic drink* The Love Potion, a painting...

. By the first century A.D. Dioscorides recognized wine of mandrake as an anaesthetic for treatment of pain or sleeplessness, to be given prior to surgery or cautery. The use of Solanaceae
Solanaceae
Solanaceae are a family of flowering plants that include a number of important agricultural crops as well as many toxic plants. The name of the family comes from the Latin Solanum "the nightshade plant", but the further etymology of that word is unclear...

 containing tropane
Tropane
Tropane is a nitrogenous bicyclic organic compound. It is mainly known for a group of alkaloids derived from it , which include, among others, atropine and cocaine. Both alkaloids contain tropinone from which tropane is a derivate...

 alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...

s for anesthesia, often in combination with opium
Opium
Opium is the dried latex obtained from the opium poppy . Opium contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine...

, persisted throughout the Roman and Islamic Empires and continued in Europe until superseded by the use of ether
Ether
Ethers are a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R'. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...

, chloroform
Chloroform
Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...

, and other modern anesthetics.

Atropine extracts from the Egyptian henbane
Henbane
Henbane , also known as stinking nightshade or black henbane, is a plant of the family Solanaceae that originated in Eurasia, though it is now globally distributed.-Toxicity and historical usage:...

 were used by Cleopatra in the last century B.C. to dilate her pupils, in the hope that she would appear more alluring. In the Renaissance
Renaissance
The Renaissance was a cultural movement that spanned roughly the 14th to the 17th century, beginning in Italy in the Late Middle Ages and later spreading to the rest of Europe. The term is also used more loosely to refer to the historical era, but since the changes of the Renaissance were not...

, women used the juice of the berries of Atropa belladonna to enlarge the pupils of their eyes, for cosmetic reasons; "bella donna" is Italian for "beautiful lady". This practice resumed briefly in the late nineteenth- and early twentieth-century in Paris.

The mydriatic effects of atropine were studied among others by the German
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...

 chemist
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....

 Friedlieb Ferdinand Runge (1795–1867). In 1831, the pharmacist Mein succeeded the pure crystalline isolation of atropine. The substance was first synthesized by German chemist Richard Willstätter
Richard Willstätter
Richard Martin Willstätter was a German organic chemist whose study of the structure of plant pigments, chlorophyll included, won him the 1915 Nobel Prize for Chemistry. Willstätter invented paper chromatography independently of Mikhail Tsvet.-Biography:Willstätter was born in to a Jewish family...

 in 1901.

Natural sources


Atropine is found in many members of the Solanaceae
Solanaceae
Solanaceae are a family of flowering plants that include a number of important agricultural crops as well as many toxic plants. The name of the family comes from the Latin Solanum "the nightshade plant", but the further etymology of that word is unclear...

 family. The most commonly-found sources are Atropa belladonna, Datura inoxia
Datura inoxia
Datura inoxia is a species in the family Solanaceae. It is native to Central and South America, and introduced in Africa, Asia, Australia and Europe. The scientific name is often cited as D. innoxia...

, D. metel
Datura metel
Datura metel is a shrub-like perennial herb, commonly known as angel's trumpet, devil's trumpet, and metel.Datura metel grows in the wild in all the warmer parts of the world, and is cultivated worldwide for its chemical and ornamental properties...

, and D. stramonium
Datura stramonium
Datura stramonium, known by the common names Jimson weed, devil's trumpet, devil's weed, thorn apple, tolguacha, Jamestown weed, stinkweed, locoweed, datura, pricklyburr, devil's cucumber, Hell's Bells, moonflower and, in South Africa, malpitte and mad seeds, is a common weed in the...

. Other sources include members of the Brugmansia
Brugmansia
Brugmansia is a genus of seven species of flowering plants in the family Solanaceae, native to subtropical regions of South America, along the Andes from Colombia to northern Chile, and also in southeastern Brazil. They are known as Angel's Trumpets, sharing that name with the closely related genus...

and Hyoscyamus
Hyoscyamus
Hyoscyamus is a small genus of flowering plants in the nightshade family, Solanaceae. The eleven species it contains are known generally as the henbanes. All of them are toxic.-Selected species:* Hyoscyamus albus L. – White Henbane...

genera. The Nicotiana
Nicotiana
Nicotiana is a genus of herbs and shrubs of the nightshade family indigenous to North and South America, Australia, south west Africa and the South Pacific. Various Nicotiana species, commonly referred to as tobacco plants, are cultivated and grown to produce tobacco. Of all Nicotiana species,...

genus (including the tobacco plant, N. tabacum
Nicotiana tabacum
Nicotiana tabacum, or cultivated tobacco, is a perennial herbaceous plant. It is found only in cultivation, where it is the most commonly grown of all plants in the Nicotiana genus, and its leaves are commercially grown in many countries to be processed into tobacco. It grows to heights between 1...

) is also found in the Solanaceae family, but these plants do not contain atropine or other tropane alkaloids.

Synthesis


Atropine can be synthesized by the reaction of tropine
Tropine
Tropine is a derivative of tropane containing a hydroxyl group at third carbon. It is also called 3-tropanol.Benzatropine and etybenzatropine are derivatives of tropine. It is also a building block of atropine, a cholinergic drug prototypical of the muscarinic antagonist class.-External Links:*...

 with tropic acid
Tropic acid
Tropic acid is a chemical with IUPAC name 3-hydroxy-2-phenylpropanoic acid and condensed structural formula HOCH2CHPhCOOH. It is a laboratory reagent used in the chemical synthesis of atropine and hyoscyamine. Tropic acid is a chiral substance, existing as either a racemic mixture or as a single...

in the presence of hydrochloric acid.

External links