Hyoscyamine

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

Overview

Hyoscyamine belongs to Deliriants.

Key safety note: Hyoscyamine and the belladonna-alkaloid plants that contain it are dangerous in overdose.[4]
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 therapeutic (antispasmodic) doses: reduced gut and bladder cramping and secretions, commonly with dry mouth, blurred near vision, constipation, difficulty urinating and a faster heartbeat.
  • At higher or toxic exposures: a deliriant state: confusion, disorientation, agitation and vivid, often frightening hallucinations that feel indistinguishable from reality, usually with amnesia for the episode.
  • Autonomic signs dominate throughout: dilated pupils, flushed dry skin, raised temperature, urinary retention and tachycardia. Effects are long-lasting (many hours, sometimes a day or more) because vision and cognition recover slowly.
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.

Not reported

Dose ranges

Duration

Chemical & Physical Properties
FormulaC17H23NO3
Molar mass289.4 g/mol
StateNot reported
Melting pointNot reported
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKaNot reported
LogP1.8 (predicted, XLogP3)
SolubilityNot reported
Refractive indexNot reported
Identifiers & Synonyms
CASNot reported
CAS (enantiomer)
PubChem CID154417
InChIKeyRKUNBYITZUJHSG-VFSICIBPSA-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-/m1/s1
SMILESCN1C2CCC1CC(OC(=O)[C@@H](CO)c1ccccc1)C2

Synonyms

    Pharmacodynamics & Biochemistry

    Hyoscyamine is a tropane-alkaloid anticholinergic and the pharmacologically active (S)-(levorotatory) enantiomer of atropine: atropine is the racemate (±)-hyoscyamine, and almost all of atropine's antimuscarinic activity resides in this (S)-form. It occurs naturally in nightshade-family plants (deadly nightshade/belladonna, henbane, datura/jimsonweed, mandrake) and is used medically as an antispasmodic (e.g. Levsin, Levbid). It is a competitive antagonist at all five muscarinic acetylcholine receptor subtypes (M1–M5), binding with subnanomolar affinity and little subtype selectivity. Blocking muscarinic receptors reduces parasympathetic ('rest and digest') tone: peripherally it relaxes smooth muscle and cuts secretions and gut/bladder spasm, speeds the heart and dilates the pupils, while blockade of brain muscarinic receptors produces the central deliriant effects. At toxic exposures it produces the classic anticholinergic toxidrome: summarised as 'blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone, full as a flask': blurred vision and dilated pupils, confusion, agitation, hallucinations and delirium, flushed skin, hyperthermia, dry mouth and skin, urinary retention and tachycardia. The quantitative receptor-affinity figures shown below are from atropine (the racemate) as the standard proxy, because the (R)-enantiomer is nearly inactive, hyoscyamine itself carries essentially the same broad, subnanomolar muscarinic antagonism.

    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
    BioavailabilityOral ≈50–80% (variable)
    Tmax≈0.5–1 h (oral)
    Half-life≈3–5 h
    VdNot reported
    Protein bindingNot reported
    MetabolismPartial hepatic hydrolysis to tropic acid and tropine. A substantial fraction is not metabolised
    ExcretionRenal: roughly half excreted unchanged in urine
    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

    Hyoscyamine and the belladonna-alkaloid plants that contain it are dangerous in overdose. Excess exposure causes the anticholinergic toxidrome: agitation, confusion, frightening hallucinations and delirium, dilated pupils and blurred vision, flushed dry skin, high fever, urinary retention and a fast heartbeat, which can progress to seizures, dangerous arrhythmias, coma and death. Hyperthermia is a particular killer. Deliriant experiences are typically dysphoric, amnesic and genuinely delirious, people cannot tell hallucination from reality and may injure themselves, which is why these substances have little recreational following. Plant material (datura/jimsonweed, belladonna) is especially dangerous because alkaloid content varies enormously between plants and even between parts of one plant, so an apparently small amount can be lethal. The antidote for severe anticholinergic delirium is physostigmine, given only under medical supervision.[4]

    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 sedating antihistamines, tricyclics, some antipsychotics and other antispasmodics: a common cause of accidental toxidrome.[4]
    Alcohol, Stimulants (amphetamines, cocaine) Alcohol and CNS depressants add sedation and confusion, while stimulants worsen hyperthermia and tachycardia.[4]
    QT-prolonging drugs (some antipsychotics, antibiotics, antiarrhythmics) Adds to the tachycardia of sympathomimetics, and caution is needed with agents that prolong the QT interval.[4]

    Contraindications

    Closed-angle glaucoma narrow-angle glaucoma (can precipitate an acute attack).[4][2]
    Pre-existing bladder or urinary-tract disease, or drug-induced cystitis urinary retention or bladder-outlet obstruction (e.g. prostatic enlargement).[4][2]
    Paralytic ileus or gastrointestinal obstruction gastrointestinal obstruction, paralytic ileus, or severe ulcerative colitis or toxic megacolon.[2]
    Myasthenia gravis[4][2]
    Cardiovascular disease, hypertension or arrhythmia tachyarrhythmia or coronary disease, with caution in the elderly.[4][2]
    Hot, dehydrating environments (overheating risk) hot environments (impaired sweating raises heatstroke risk).[4]
    Usage & Context
    • Medically used as an antispasmodic for gastrointestinal and bladder spasm and as a drying/pre-anaesthetic agent, at low prescription doses (e.g. Levsin, Levbid, also in combination products).
    • A principal toxic alkaloid of nightshade-family plants (belladonna, henbane, datura/jimsonweed, mandrake), responsible for accidental and deliberate poisonings.
    • Occasionally taken as a deliriant, almost always via those plants, but its dysphoric, amnesic and dangerous profile gives it little recreational appeal.
    Sources & Evidence
    1. PubChem: Hyoscyamine (CID 154417) — identifiers & computed properties
    2. FDA / DailyMed: Hyoscyamine prescribing information — pharmacokinetics & metabolism
    3. Drugs@FDA (U.S. Food & Drug Administration): hyoscyamine products — prescription-only medicine, not a controlled substance
    4. Broderick ED, Metheny KE, Crosby B. Anticholinergic Toxicity. StatPearls [Internet] (NCBI Bookshelf, NBK534798) — anticholinergic toxidrome, clinical features & management
    5. IUPHAR/BPS Guide to PHARMACOLOGY: atropine (ligand 320) — muscarinic M1–M5 antagonist binding data (proxy for hyoscyamine, its active (S)-enantiomer) CC BY-SA 4.0
    6. Wikipedia: Hyoscyamine (chemistry, pharmacology & medical use) CC BY-SA 4.0
    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.

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    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

    19. PubChem computed properties (CID 154417)

    Further Information