Atropine

[(1S,5R)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate

Overview

Atropine belongs to Deliriants.

Key safety note: Atropine has a narrow margin between its useful antimuscarinic effect and toxicity.[3][2]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • At medical doses the wanted effects are peripheral: faster heart rate, dry mouth, reduced sweating, pupil dilation and relaxed smooth muscle. There is no euphoria.
  • As a recreational deliriant (via belladonna, Datura or henbane) it produces a true delirium: vivid, often frightening hallucinations that are indistinguishable from reality, with confusion, disorientation and amnesia: quite unlike the effects of psychedelics.
  • Accompanying bodily effects are uniformly unpleasant: dry mouth and skin, flushing, overheating, blurred near-vision, racing heart, urinary retention, and a hangover that can last for days.
  • Onset is roughly 30–60 minutes orally and the delirium can last many hours, with blurred vision and other effects persisting far longer.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Intravenous / intramuscular (medical), Oral, Ophthalmic. Atropine is a prescription medicine dosed by clinicians. The figures below are medical reference doses, not recreational guidance. Recreational deliriant use via belladonna/Datura/henbane is extremely dangerous: plant alkaloid content varies enormously between and within plants, so an 'effective' amount and a life-threatening one can be indistinguishable. There is no safe recreational dose.

Dose ranges

Symptomatic bradycardia (IV)

0.5–1 mg IV every 3–5 min, max ~3 mg

Organophosphate / nerve-agent poisoning

2–3 mg IV, doubling every 5–20 min, titrated to secretions (very large total doses may be needed)

Duration

onset

≈1 min IV, ≈30–60 min oral

total

Antimuscarinic effects ≈4–6 h, deliriant intoxication and blurred vision last much longer

Chemical & Physical Properties
FormulaC17H23NO3
Molar mass289.4 g/mol
StateNot reported
Melting point≈118–119 °C
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKaNot reported
LogP1.8 (predicted, XLogP3)
Solubility>43.4 µg/mL at pH 7.4 (free base). Atropine sulfate is freely water-soluble
Refractive indexNot reported
Identifiers & Synonyms
CAS51-55-8
CAS (enantiomer)
PubChem CID174174
InChIKeyRKUNBYITZUJHSG-PJPHBNEVSA-N
InChIInChI=1S/C17H23NO3/c1-18-13-7-8-14(18)10-15(9-13)21-17(20)16(11-19)12-5-3-2-4-6-12/h2-6,13-16,19H,7-11H2,1H3/t13-,14+,15?,16?
SMILESCN1[C@@H]2CC[C@H]1CC(C2)OC(=O)C(CO)C3=CC=CC=C3

Synonyms

    Pharmacodynamics & Biochemistry

    Atropine is the prototype antimuscarinic (anticholinergic) drug: a competitive, reversible antagonist at all five muscarinic acetylcholine-receptor subtypes (M1–M5), with sub-nanomolar to low-nanomolar affinity and little subtype selectivity (see the binding table). By blocking the parasympathetic actions of acetylcholine it speeds the heart, dilates the pupils, dries secretions and relaxes smooth muscle (gut, bladder, bronchi), because it is a tertiary amine that crosses the blood–brain barrier it also has central effects, including delirium at high doses. Atropine is the racemate (±)-hyoscyamine: almost all of the antimuscarinic activity resides in the (S)-(L)-enantiomer, L-hyoscyamine, while the (R)-(D)-form is largely inactive. It is a tropane alkaloid found in nightshade-family plants such as Atropa belladonna (deadly nightshade), Datura (jimsonweed) and Hyoscyamus (henbane). Clinically this antimuscarinic action is used to reverse cholinergic crisis: atropine is the standard antidote for organophosphate/nerve-agent and muscarinic (Inocybe/Clitocybe) mushroom poisoning, and to treat symptomatic bradycardia, reduce airway secretions before anaesthesia, and dilate the pupil for eye examination. The quantitative pharmacology is essentially pure muscarinic antagonism: the M1–M5 constants sit at ~0.2–3 nM, whereas the other entries in the binding table, α2A-adrenoceptor (~16 µM) and glycine receptor (~250 µM), are four to six orders of magnitude weaker, high-concentration in-vitro off-targets with no bearing on atropine's clinical or recreational effects.

    Biological targets

    • mAChR

    Binding & functional measurements

    TargetMeasurementSpecies
    M4 receptorpKi 9.7Rat
    M5 receptorpKi 9.4Rat
    M1 receptorpKi 9.35Rat
    M3 receptorpKi 9.15Human
    M4 receptorpKi 9.1Human
    M1 receptorpKi 9.05Human
    M2 receptorpKi 9.05Rat
    M3 receptorpKi 9Rat
    M5 receptorpKi 8.8Human
    M2 receptorpKi 8.5Human
    Pharmacokinetics
    Bioavailability≈25% oral, rapid and complete after IV/IM
    TmaxNot reported
    Half-life≈2–4 h
    VdNot reported
    Protein bindingNot reported
    MetabolismEster hydrolysis (≥50%) to tropine and tropic acid by hepatic and plasma esterases
    ExcretionRenal: 15–50% excreted unchanged
    Toxicology & Safety
    Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

    Not reported

    Atropine has a narrow margin between its useful antimuscarinic effect and toxicity. Overdose: from a dosing error or, dangerously, from recreational use of belladonna/Datura plants whose alkaloid content is wildly variable: produces the anticholinergic toxidrome: dilated unreactive pupils and blurred vision, dry flushed skin, hyperthermia, urinary retention, ileus, tachycardia, and an agitated, amnesic delirium with hallucinations that can progress to seizures, coma and, rarely, death ('blind as a bat, dry as a bone, red as a beet, hot as a hare, mad as a hatter'). The delirium is genuinely confusional rather than euphoric, and the hyperthermia plus dangerous behaviour make it a high-risk recreational intoxication. The antidote is the cholinesterase inhibitor physostigmine. Use cautiously in the elderly and in glaucoma, prostatic/bladder-outlet obstruction, myasthenia gravis, obstructive GI disease and heat exposure.[3][2]

    Legal Status
    Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
    Interactions & Contraindications

    Drug interactions

    Anticholinergic drugs Additive anticholinergic toxicity with antihistamines, tricyclics, antipsychotics and other antimuscarinics: worsening delirium, hyperthermia, tachycardia and ileus.[3]
    Cholinesterase inhibitors (physostigmine, donepezil, pyridostigmine, organophosphates) Pharmacological antagonists (physostigmine, pyridostigmine, donepezil, organophosphates). Physostigmine is used to reverse central anticholinergic toxicity.[3]
    QT-prolonging drugs (some antipsychotics, antibiotics, antiarrhythmics), Stimulants (amphetamines, cocaine) Drugs that raise heart rate or prolong QT, and agents that impair heat loss, add cardiovascular strain and hyperthermia risk.[3]

    Contraindications

    Closed-angle glaucoma angle-closure (narrow-angle) glaucoma.[3]
    Pre-existing bladder or urinary-tract disease, or drug-induced cystitis prostatic hypertrophy or other bladder-outlet or urinary obstruction.[3]
    Paralytic ileus or gastrointestinal obstruction obstructive gastrointestinal disease, paralytic ileus or severe ulcerative colitis.[3]
    Myasthenia gravis[3]
    Cardiovascular disease, hypertension or arrhythmia tachyarrhythmia or coronary disease, with caution in the elderly.[3]
    Hot, dehydrating environments (overheating risk) hot environments (impaired sweating).[3]
    Usage & Context
    • A frontline emergency medicine: antidote for organophosphate/nerve-agent and muscarinic mushroom poisoning, treatment of symptomatic bradycardia (ACLS), and reduction of secretions before anaesthesia: on the WHO Model List of Essential Medicines.
    • In ophthalmology as long-acting mydriatic/cycloplegic drops, and in low doses to slow the progression of childhood myopia.
    • Recreationally and historically as a deliriant and poison via nightshade plants (belladonna, Datura, henbane): tied to 'witches' flying ointments' and to accidental poisonings. Such use is uncommon and widely regarded as unpleasant and dangerous.
    Sources & Evidence
    1. PubChem: Atropine (CID 174174) — identifiers & computed properties
    2. Wikipedia: Atropine (pharmacology, effects, PK & legal status) CC BY-SA 4.0
    3. McLendon K, Preuss CV. Atropine. StatPearls [Internet] (NCBI Bookshelf, NBK470551) — mechanism, dosing, toxicity & contraindications
    4. IUPHAR/BPS Guide to PHARMACOLOGY: atropine (ligand 320) — muscarinic M1–M5 binding data CC BY-SA 4.0
    5. Carr BJ, Mihara K, Ramachandran R, et al. (2018). Myopia-Inhibiting Concentrations of Muscarinic Receptor Antagonists Block Activation of Alpha2A-Adrenoceptors In Vitro. Invest Ophthalmol Vis Sci 59:2778-2791.

      PMID 29860464 · doi:10.1167/iovs.17-22562

    6. Maksay G, Laube B, Betz H (1999). Selective blocking effects of tropisetron and atropine on recombinant glycine receptors. J Neurochem 73:802-6.

      PMID 10428078 · doi:10.1046/j.1471-4159.1999.0730802.x

    7. Kashihara K, Varga EV, Waite SL, et al. (1992). Cloning of the rat M3, M4 and M5 muscarinic acetylcholine receptor genes by the polymerase chain reaction (PCR) and the pharmacological characterization of the expressed genes. Life Sci 51:955-71.

      PMID 1325587 · doi:10.1016/0024-3205(92)90403-c

    8. Peralta EG, Ashkenazi A, Winslow JW, et al. (1987). Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J 6:3923-9.

      PMID 3443095 · doi:10.1002/j.1460-2075.1987.tb02733.x

    9. Moriya H, Takagi Y, Nakanishi T, et al. (1999). Affinity profiles of various muscarinic antagonists for cloned human muscarinic acetylcholine receptor (mAChR) subtypes and mAChRs in rat heart and submandibular gland. Life Sci 64:2351-8.

      PMID 10374898 · doi:10.1016/s0024-3205(99)00188-5

    10. Buckley NJ, Bonner TI, Buckley CM, et al. (1989). Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells. Mol Pharmacol 35:469-76.

      PMID 2704370

    11. Cheng K, Khurana S, Chen Y, et al. (2002). Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist. J Pharmacol Exp Ther 303:29-35.

      PMID 12235229 · doi:10.1124/jpet.102.036376

    12. Hirose H, Aoki I, Kimura T, et al. (2001). Pharmacological properties of (2R)-N-[1-(6-aminopyridin-2-ylmethyl)piperidin-4-yl]-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide: a novel mucarinic antagonist with M(2)-sparing antagonistic activity. J Pharmacol Exp Ther 297:790-7.

      PMID 11303071

    13. Huang F, Buchwald P, Browne CE, et al. (2001). Receptor binding studies of soft anticholinergic agents. AAPS PharmSci 3:E30.

      PMID 12049493 · doi:10.1208/ps030430

    14. Croy CH, Chan WY, Castetter AM, et al. (2016). Characterization of PCS1055, a novel muscarinic M4 receptor antagonist. Eur J Pharmacol 782:70-6.

      PMID 27085897 · doi:10.1016/j.ejphar.2016.04.022

    15. Smith CM, Wallis RM (1997). Characterisation of [3H]-darifenacin as a novel radioligand for the study of muscarinic M3 receptors. J Recept Signal Transduct Res 17:177-84.

      PMID 9029489 · doi:10.3109/10799899709036602

    16. Christopoulos A, Pierce TL, Sorman JL, et al. (1998). On the unique binding and activating properties of xanomeline at the M1 muscarinic acetylcholine receptor. Mol Pharmacol 53:1120-30.

      PMID 9614217

    17. Fruchart-Gaillard C, Mourier G, Marquer C, et al. (2006). Identification of various allosteric interaction sites on M1 muscarinic receptor using 125I-Met35-oxidized muscarinic toxin 7. Mol Pharmacol 69:1641-51.

      PMID 16439611 · doi:10.1124/mol.105.020883

    18. Kovacs I, Yamamura HI, Waite SL, et al. (1998). Pharmacological comparison of the cloned human and rat M2 muscarinic receptor genes expressed in the murine fibroblast (B82) cell line. J Pharmacol Exp Ther 284:500-7.

      PMID 9454790

    Further Information