Pentobarbital

5-ethyl-5-pentan-2-yl-1,3-diazinane-2,4,6-trione

Overview

Pentobarbital belongs to Depressants.

Key safety note: Pentobarbital has a low therapeutic index and no ceiling on respiratory depression, so the difference between a sedative, an anaesthetic and a fatal dose is small.[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.
  • Sedation, anxiety relief, drowsiness and, at higher doses, sleep. Disinhibition and a 'drunk' euphoria some seek recreationally.
  • Slurred speech, poor coordination, impaired memory and judgement.
  • With regular use: rapid tolerance, physical dependence, and a dangerous withdrawal (tremor, seizures) on stopping.
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.

Oral, and by injection (IV/IM) or rectally: clinician-administered. Figures below are clinical context, NOT a recreational guide. Pentobarbital is used deliberately to end life and there is no safe recreational dose.. Pentobarbital's effect runs on a steep continuum from sedation to anaesthesia to fatal respiratory arrest, with only a small margin between them, and the margin narrows with tolerance and with any other depressant. There is no ceiling effect and no antidote. It must never be stopped abruptly after regular use.

Dose ranges

Sedative/hypnotic (historical, oral)

≈100 mg at bedtime (adult)

Barbiturate coma (ICU)

IV loading + infusion, specialist-titrated to EEG

Duration

onset

Oral ≈15–60 min, IV within minutes

total

Hypnotic effect ≈3–6 h (elimination half-life ≈15–48 h)

after effects

Residual sedation/'hangover'. Withdrawal on cessation after regular use

Chemical & Physical Properties
FormulaC11H18N2O3
Molar mass226.27 g/mol
StateSolid
Melting point129.5 °C
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKa8.11 (25 °C)
LogP2.1
Solubility679 mg/L (at 25 °C), Pentobarbital sodium: a white, hygroscopic, crystalline powder or granules, odourless or with a slight characteristic odour and a slightly bitter taste. Very soluble in water and alcohol. Practically insoluble in ether. A 10% solution in water has pH 9.6–11 and slowly decomposes., Pentobarbital calcium: a fine, white, odourless, crystalline powder with a slightly bitter taste. Sparingly soluble in water. Slightly soluble in alcohol. Practically insoluble in ether. A saturated solution in water has pH about 9.5.
Refractive indexNot reported
Identifiers & Synonyms
CAS76-74-4
CAS (enantiomer)
PubChem CID4737
InChIKeyWEXRUCMBJFQVBZ-UHFFFAOYSA-N
InChIInChI=1S/C11H18N2O3/c1-4-6-7(3)11(5-2)8(14)12-10(16)13-9(11)15/h7H,4-6H2,1-3H3,(H2,12,13,14,15,16)
SMILESCCCC(C)C1(C(=O)NC(=O)NC1=O)CC

Synonyms

    Pharmacodynamics & Biochemistry

    Pentobarbital (Nembutal) is a short-to-intermediate-acting barbiturate. It is a positive allosteric modulator of the GABA-A receptor: it binds the barbiturate site and increases the duration of chloride-channel opening in response to GABA, and at higher concentrations it opens the channel directly, independent of GABA. This direct action is why barbiturates, unlike benzodiazepines, have no ceiling to their sedative and respiratory depression: the basis of both their anaesthetic use and their lethality. Its effects run along a dose continuum from anxiolysis and sedation through hypnosis to general anaesthesia, coma and death. It is well absorbed orally (bioavailability ≈70–90%) and metabolised in the liver, with a half-life of roughly 15–48 hours. Onset is faster and duration shorter than phenobarbital's. Because a controlled, reliably lethal dose produces deep coma and painless respiratory arrest, pentobarbital sodium is the agent of choice for animal euthanasia and is widely used in physician-assisted dying and in capital-punishment lethal injection. In intensive care a 'pentobarbital coma' is used to control refractory status epilepticus and dangerously raised intracranial pressure.

    Biological targets

    • GABA-A
    Pharmacokinetics
    BioavailabilityOral ≈70–90% (rectal ≈90%)
    TmaxNot reported
    Half-life≈15–48 h
    VdNot reported
    Protein binding≈20–45%
    MetabolismHepatic
    ExcretionRenal
    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

    Pentobarbital has a low therapeutic index and no ceiling on respiratory depression, so the difference between a sedative, an anaesthetic and a fatal dose is small. It causes death by respiratory arrest, and indeed it is used deliberately for euthanasia and lethal injection. The danger is multiplied by alcohol, opioids and benzodiazepines. There is no specific antidote (flumazenil does not reverse barbiturates). Overdose care is supportive (airway/ventilatory and circulatory support). Regular use produces tolerance and physical dependence, and abrupt withdrawal is dangerous: a syndrome like severe alcohol/benzodiazepine withdrawal with agitation, tremor, seizures and delirium that can be fatal and requires a slow taper. Never use non-medically.[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

    Alcohol, Opioids, Benzodiazepines Additive, potentially fatal respiratory depression.[2]
    Drugs cleared by induced liver enzymes (warfarin, oral contraceptives, many antiepileptics, corticosteroids) Hepatic enzyme induction can reduce the effect of drugs such as warfarin and oral contraceptives.[2]

    Contraindications

    Significant respiratory depression or acute severe asthma severe respiratory depression or respiratory disease.[2]
    Acute intermittent or related porphyria[2]
    Kidney or liver impairment severe hepatic impairment.[2]
    Combining with alcohol or other CNS depressants[2]
    Known hypersensitivity to the drug barbiturate hypersensitivity.[2]
    Usage & Context
    • A short/intermediate-acting barbiturate (Nembutal) once widely used as a sedative and sleeping pill, now largely replaced by benzodiazepines for that purpose.
    • Current uses are mostly at the extremes: control of refractory status epilepticus and raised intracranial pressure ('pentobarbital coma') in intensive care, and, as pentobarbital sodium, veterinary euthanasia, physician-assisted dying and capital-punishment lethal injection.
    • Diverted 'Nembutal' is also sought illicitly, notably for suicide.
    Sources & Evidence

    Further Information