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Atropine is the prototypical antimuscarinic xenobiotic. It is a competitive antagonist at both central and peripheral muscarinic receptors, that is used to treat patients with symptoms following exposures to muscarinic agonists such as pilocarpine, Clitocybe mushrooms, and acetylcholinesterase inhibitors. The latter group includes pesticides, such as carbamate and organic phosphorous compounds, chemical warfare nerve agents, and some xenobiotics used to treat patients with Alzheimer disease, such as donepezil and rivastigmine.


Many plants contain the alkaloids atropine and or scopolamine. One notable example is Atropa belladonna, named by Linnaeus after Atropos, the goddess of fate in Greek mythology who could cut short a person’s life. Belladonna means beautiful woman in Italian and comes from the practice by Italian women of placing belladonna extract in their eyes to produce aesthetically pleasing dilated pupils.10 In the early 1800s, atropine was isolated and purified from plants. In the 1860s, Fraser experimented with the dose–response relationship between atropine and physostigmine involving various organs such as the heart and the eye.20 Experiments in the 1940s with cholinesterase inhibitors demonstrated that atropine reversed many of the effects of these xenobiotics and protected animals against doses two to three times the LD50.50



Atropine (dl-hyoscyamine), like scopolamine (l-hyoscine), is a tropane alkaloid with a tertiary amine structure that allows central nervous system (CNS) penetration. Quaternary amine antimuscarinics such as glycopyrrolate, ipratropium, tiotropium, methylhomatropine bromide, and methylatropine bromide do not cross the blood–brain barrier into the CNS. Tropane alkaloids are bicyclic nitrogen containing compounds that are naturally found in the plants of the families Solanaceae (eg, deadly nightshade, Datura) and Erythroxylaceae (eg, coca) and have a long history of use as poisons and medicinals. Only l-hyoscyamine is active and found in nature. The process of isolation results in racemization and forms dl-hyoscyamine.

Mechanism of Action

Cholinergic receptors consist of muscarinic and nicotinic subtypes. Muscarinic receptors are coupled to G proteins and either inhibit adenylyl cyclase (M2, M4) or increase phospholipase C (M1, M3, M5). Muscarinic receptors are widely distributed throughout the peripheral and central nervous systems.23

The competitive blockade of muscarinic receptors in normal indivi­duals results in dose-dependent clinical effects that vary by organ system based on the degree of endogenous parasympathetic tone.10,23 In adults, low doses (0.5 mg) of atropine sometimes causes a paradoxical bradycardia of about 4 to 8 beats per minute, not evident with rapid IV administration. Higher doses of atropine (2 mg) produce noticeable dryness of the mouth and sweat glands, feeling of warmth, flushing, tachycardia, reactive dilated pupils, blurred near vision, drowsiness, postural hypotension, and urinary hesitation. At higher doses (3 to ...

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