The name atropine was coined in the 19th century, when pure extracts from the belladonna plant Atropa belladonna were first made. The medicinal use of preparations from plants in the nightshade family is much older. Mandragora (mandrake) was described by Theophrastus in the fourth century B.C. for treatment of wounds, gout, and sleeplessness, and as a love potion. By the first century A.D. Dioscorides recognized wine of mandrake as an anesthetic for treatment of pain or sleeplessness, to be given prior to surgery or cautery. The use of nightshade preparations for anesthesia, often in combination with opium, persisted throughout the Roman and Islamic Empires and continued in Europe until superseded in the 19th century by modern anesthetics.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 plant (another nightshade) were used by Cleopatra in the last century B.C. to dilate the pupils of her eyes, in the hope that she would appear more alluring. Likewise in the Renaissance, women used the juice of the berries of the nightshade Atropa belladonna to enlarge their pupils for cosmetic reasons. This practice resumed briefly in the late nineteenth and early twentieth century in Paris. The pharmacological study of belladonna extracts was begun by the German chemist 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 in 1901.
In general, atropine counters the “rest and digest” activity of glands regulated by the parasympathetic nervous system. This occurs because atropine is a competitive, reversible antagonist of the muscarinic acetylcholine receptors (acetylcholine being the main neurotransmitter used by the parasympathetic nervous system). Atropine is a competitive antagonist of the muscarinic acetylcholine receptor types M1, M2, M3, M4 and M5. It is classified as an anticholinergic drug (parasympatholytic). Atropine, a tropane alkaloid, is an enantiomeric mixture of d-hyoscyamine and l-hyoscyamine, with most of its physiological effects due to l-hyoscyamine. Its pharmacological effects are due to binding to muscarinic acetylcholine receptors. 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. 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 (monohydrate) (C 17H 23NO 3)2·H2SO4·H2O, the full chemical name is 1α H, 5α H-Tropan-3-α ol (±)-tropate(ester), sulfate monohydrate.
Topical atropine is used as a cycloplegic, to temporarily paralyze the accommodation reflex, and as a mydriatic, to dilate the pupils. Atropine degrades slowly, typically wearing off in 7 to 14 days, so it is generally used as a therapeutic mydriatic, whereas tropicamide (a shorter-acting cholinergic antagonist) or phenylephrine (an α-adrenergic agonist) is preferred as an aid to ophthalmic examination.
In refractive and accommodative amblyopia, 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.
Atropine has been noted as being effective in slowing myopia progression in children. Research has shown that while higher dosages (1.0%) are more effective at slowing myopia, the side effects and high rebound effect have made its adoption impractical. Lower dosages ranging from 0.5% to 0.01% have been shown to slow myopia as well, with fewer side effects. The lower dose of 0.01% is thus generally recommended due to less side effects and potential less rebound worsening when the atropine is stopped. The most common adverse effect is photophobia, others include allergy, headache, blushing, and gastrointestinal reaction. While the optimal dosage still remains elusive, many researchers feel that 0.05% strikes the right balance between effectiveness and tolerated side effects.
Adverse reactions to high dosages of atropine include ventricular fibrillation, supraventricular or ventricular tachycardia, dizziness, nausea, blurred vision, loss of balance, dilated pupils, photophobia, dry mouth and potentially extreme confusion, deliriant hallucinations, and excitation especially among the elderly. These latter effects are because atropine is able to cross the blood–brain barrier. The antidote to atropine is physostigmine or pilocarpine. A common mnemonic used to describe the physiologic manifestations of atropine overdose is: “hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter”. These associations reflect the specific changes of warm, dry skin from decreased sweating, blurry vision, decreased lacrimation, vasodilation, and central nervous system effects on muscarinic receptors, type 4 and 5. This set of symptoms is known as anticholinergic toxidrome, and may also be caused by other drugs with anticholinergic effects, such as hyoscine hydrobromide (scopolamine), diphenhydramine, phenothiazine antipsychotics and benztropine.