Scopolamine
(9-methyl-3-oxa-9-azatricyclo[3.3.1.0²,⁴]nonan-7-yl) 3-hydroxy-2-phenylpropanoate
Overview
Scopolamine belongs to Deliriants.
Effects
- At therapeutic (antiemetic / anti-motion-sickness) doses: prevention of nausea and vertigo, together with anticholinergic side effects: dry mouth, blurred vision, drowsiness, dilated pupils and a faster heartbeat.
- It is amnestic and sedating rather than euphoric. People who take it seeking psychoactivity typically report a dysphoric, confusing and frightening experience.
- At high or toxic doses: a deliriant syndrome: vivid hallucinations experienced as real, disorientation, agitation, memory loss, flushed dry skin, urinary retention, hyperthermia and, in severe cases, seizures, arrhythmia and coma.
Dosing & duration
Transdermal patch, oral, sublingual, subcutaneous, intravenous, intramuscular and ophthalmic. The transdermal patch is the usual route for motion sickness.. Scopolamine is a prescription antimuscarinic used at low doses. The figures below are therapeutic references, not recreational guidance. It is a deliriant at higher doses, not a euphoriant: anticholinergic delirium is unpleasant and dangerous (hyperthermia, seizures, arrhythmia, coma). The therapeutic window is narrow and effects are unpredictable between individuals, so there is no safe recreational dose. Combining it with other anticholinergics (many antihistamines, tricyclics, antipsychotics) compounds the toxicity.
Dose ranges
1.5 mg patch over 72 h
0.3–0.6 mg SC/IM/IV
Supra-therapeutic, unpredictable and dangerous
Duration
Transdermal ≈6–8 h to full effect, parenteral within ~30 min
Transdermal patch up to ~72 h, a single parenteral dose lasts several hours
Residual anticholinergic effects and amnesia. Blurred vision may persist
Chemical & Physical Properties
| Formula | C17H21NO4 |
| Molar mass | 303.35 g/mol |
| State | Solid (usually the hydrobromide salt, white crystalline powder, free base is a viscous, low-melting solid) |
| Melting point | ≈59 °C (free base), ≈195 °C (hydrobromide) |
| Boiling point | Not reported |
| Density | Not reported |
| Vapor pressure | Not reported |
| pKa | ≈7.5–7.8 (tertiary amine) |
| LogP | 0.9 (predicted, XLogP3) |
| Solubility | Hydrobromide: freely soluble in water, soluble in ethanol, Free base: soluble in water, ethanol, ether and chloroform |
| Refractive index | Not reported |
Identifiers & Synonyms
| CAS | 51-34-3 |
| CAS (enantiomer) | |
| PubChem CID | 5184 |
| InChIKey | STECJAGHUSJQJN-UHFFFAOYSA-N |
| InChI | InChI=1S/C17H21NO4/c1-18-13-7-11(8-14(18)16-15(13)22-16)21-17(20)12(9-19)10-5-3-2-4-6-10/h2-6,11-16,19H,7-9H2,1H3 |
| SMILES | CN1C2C[C@@H](OC(=O)C(CO)c3ccccc3)CC1[C@@H]1O[C@H]21 |
Synonyms
- Hyoscine
- Devil's Breath
- (−)-scopolamine
Pharmacodynamics & Biochemistry
Scopolamine (hyoscine) is a naturally occurring tropane alkaloid, the (–)-isomer, that acts as a competitive antagonist at muscarinic acetylcholine receptors (an antimuscarinic/anticholinergic). Unlike its quaternary derivative butylscopolamine, it is a tertiary amine that readily crosses the blood–brain barrier, so it has marked central as well as peripheral effects. It is a high-affinity, non-selective antagonist across all five muscarinic subtypes (M1–M5), with sub-nanomolar to low-nanomolar affinity (human pKi ≈8.7–9.4). Blocking central muscarinic transmission underlies its anti-motion-sickness, antiemetic, amnestic and, at higher doses, deliriant effects, while peripheral blockade produces the classic anticholinergic signs: dry mouth, dilated pupils, fast heartbeat, reduced secretions and urinary retention. At toxic doses it produces a full central anticholinergic syndrome, confusion, agitation, hallucinations and delirium with amnesia, which is the basis of its reputation as a deliriant and of its criminal use ('Devil's Breath') to incapacitate victims and render them suggestible and amnesic.
Biological targets
- M1
- M2
- M3
- M4
- M5
Binding & functional measurements
| Target | Measurement | Species |
|---|---|---|
| M3 receptor | pKi 9.4 | Human |
| M4 receptor | pKi 9.3 | Human |
| M1 receptor | pKi 9 | Human |
| M2 receptor | pKi 8.7 | Human |
| M5 receptor | pKi 8.7 | Human |
Pharmacokinetics
| Bioavailability | Oral ~20–40% (low, extensive first-pass), transdermal delivery is used to give steady plasma levels |
| Tmax | Transdermal effect builds over several hours, parenteral effect within ~30 min |
| Half-life | ≈5 h |
| Vd | Not reported |
| Protein binding | Not reported |
| Metabolism | Hepatic (CYP3A4) |
| Excretion | Renal (largely as metabolites) |
Toxicology & Safety
Not reported
Scopolamine is safe and effective at the low doses used for motion sickness and nausea, but it has a narrow margin and is dangerous in overdose. Anticholinergic toxicity produces the classic picture: 'blind as a bat, dry as a bone, red as a beet, hot as a hare, mad as a hatter': dilated pupils and blurred vision, dry flushed skin, fever, and an agitated delirium with hallucinations and amnesia that can progress to seizures, arrhythmia and coma. The elderly are especially susceptible. It is not a euphoriant: its deliriant, amnesic and incapacitating effects are the basis of its criminal use as 'Devil's Breath' (burundanga). Toxicity is additive with other anticholinergic drugs, of which many antihistamines, tricyclics and antipsychotics are examples.[6][7]
Legal Status
US: Prescription only (Rx). UK: Prescription only (POM) / P. DE: Prescription only (Rx)
Interactions & Contraindications
Drug interactions
Contraindications
No interactions or contraindications listed.
Usage & Context
- A widely used antimuscarinic medicine: transdermal patches for motion sickness and postoperative nausea, injectable hyoscine to reduce secretions (anaesthetic premedication, palliative 'death rattle') and for antiemesis, and ophthalmic use as a mydriatic/cycloplegic.
- Also historically and criminally significant: as a deliriant it has been used (as 'Devil's Breath' / burundanga) to incapacitate victims for robbery or assault, exploiting the amnesia and suggestibility it produces. Recreational use is uncommon and generally dysphoric.
Sources & Evidence
- PubChem: Scopolamine (CID 5184) — identifiers & computed properties
- IUPHAR/BPS Guide to PHARMACOLOGY: scopolamine (ligand 330) — human M1–M5 antagonist affinities CC BY-SA 4.0
- Bolden C, Cusack B, Richelson E (1992). Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther 260:576-80.
PMID 1346637
- 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
- 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
- Renner UD, Oertel R, Kirch W (2005). Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. Ther Drug Monit 27:655-65.
PMID 16175141 · doi:10.1097/01.ftd.0000168293.48226.57
- Wikipedia: Scopolamine (medical use, toxicity, 'Devil's Breath' & legal status) CC BY-SA 4.0