atropine

atropine
Name	Atropine
IUPAC name	(RS)-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl) 3-hydroxy-2-phenylpropanoate
CAS number	51-55-8
PubChem	174174
DrugBank	DB00572
ChemSpiderID	10194105
UNII	7C0697DR9I
ChEMBL	CHEMBL1201209
ATC prefix	A03
ATC suffix	BA01
ATC supplemental	S01FA01

atropine is a naturally occurring tropane alkaloid extracted from plants of the Solanaceae family, such as deadly nightshade (Atropa belladonna), jimson weed (Datura stramonium), and mandrake. It functions as a competitive antagonist of muscarinic acetylcholine receptors, leading to widespread anticholinergic effects throughout the central nervous system and parasympathetic nervous system. This agent has been employed for centuries, with historical uses ranging from cosmetics to poisons, and is now a critical tool in modern anesthesiology, ophthalmology, and the management of organophosphate poisoning.

Chemical properties and structure

The molecular structure of atropine is characterized by a complex tropane ring system, specifically a fused bicyclic compound comprising a piperidine ring and a pyrrolidine ring. This core structure is esterified with tropic acid, which contains an aromatic phenyl group; the compound exists as a racemic mixture of two enantiomers, with the biologically active form being hyoscyamine. Its synthesis was first achieved by Richard Willstätter in 1901, marking a significant milestone in organic chemistry. The compound forms white crystalline salts, such as atropine sulfate, which are highly soluble in water and ethanol, a property essential for its formulation into injectable solutions and ophthalmic drops.

Medical uses

In contemporary clinical practice, atropine is indispensable for pre-anesthetic medication to reduce salivary and bronchial secretions and to prevent bradycardia during surgery. It is a mainstay in advanced cardiac life support protocols for treating symptomatic bradyarrhythmias and in the initial management of organophosphate and nerve agent intoxication, such as from sarin or VX. Ophthalmologists utilize it as a mydriatic and cycloplegic agent to facilitate examinations of the retina and for treating conditions like uveitis. Furthermore, it is used to alleviate bradycardia associated with myocardial infarction and is included in the World Health Organization Model List of Essential Medicines.

Mechanism of action

Atropine exerts its effects by competitively blocking acetylcholine from binding to muscarinic acetylcholine receptors (M1-M5 subtypes) located on effector organs innervated by the parasympathetic nervous system. This blockade inhibits the normal autonomic nervous system responses, leading to increased heart rate, decreased gastrointestinal tract motility, and relaxation of smooth muscle in the bronchi and urinary bladder. Its action in the central nervous system, particularly at the medulla oblongata and higher centers, can produce delirium at high doses. The specificity of its antagonism was elucidated through the pioneering work of John Newport Langley and Paul Ehrlich on receptor theory.

Side effects and toxicity

Common adverse effects, resulting from its systemic anticholinergic action, include xerostomia (dry mouth), mydriasis (dilated pupils), tachycardia, urinary retention, and decreased sweat gland activity leading to hyperthermia. Acute atropine poisoning, which can result from ingestion of plants like deadly nightshade, presents as the classic anticholinergic toxidrome: hot, dry, red skin; hyperthermia; tachycardia; ileus; delirium; and hallucinations, often memorably described as "blind as a bat, dry as a bone, red as a beet, hot as hell, and mad as a hatter." Treatment is primarily supportive, with the acetylcholinesterase inhibitor physostigmine serving as a specific antidote in severe cases.

History and sources

The use of atropine-containing plants predates recorded history, with references found in works by Dioscorides and in the witch ointments of medieval Europe. Its name derives from Atropos, one of the three Fates in Greek mythology who cut the thread of life, reflecting its lethal potential. The compound was first isolated in pure form in 1831 by the German pharmacist Heinrich F. G. Mein, and its structural elucidation was advanced by Willstätter. During the Cold War, atropine auto-injectors like the ComboPen became standard issue for NATO forces as a countermeasure against chemical warfare agents.

Society and culture

Atropine has a rich and often sinister cultural history, famously associated with the Italian Renaissance practice of using belladonna extract to dilate pupils for cosmetic effect, as depicted in paintings from the Florentine school. It has been implicated in historical poisonings, including the alleged use of "Aqua Tofana" in 17th-century Italy. In literature, its effects are referenced in works like Nathaniel Hawthorne's "Rappaccini's Daughter." Modern depictions appear in films and television series involving chemical weapons, such as *The Rock*. Its inclusion on the World Health Organization Model List of Essential Medicines underscores its global medical importance, while its production remains tightly regulated under treaties like the Chemical Weapons Convention.

Category:Anticholinergics Category:Alkaloids Category:World Health Organization essential medicines