Propofol

2,6-di(propan-2-yl)phenol

Overview

Propofol belongs to Anesthetics.

Key safety note: Propofol is one of the most widely used intravenous anaesthetics, but it is dangerous outside a controlled clinical setting.[3][6]
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.
  • Rapid onset of sedation, then hypnosis and, at anaesthetic doses, unconsciousness within about a minute of intravenous injection. Recovery is fast and often described as clear-headed, sometimes with mild euphoria or a sense of well-being on emergence.
  • It produces no analgesia, pain is not blunted, and the injection itself is often painful. Amnesia for the period of sedation is typical.
  • Dose-dependent respiratory depression (progressing to apnoea) and a fall in blood pressure accompany hypnotic doses. There is no safe recreational dose and no reversal agent.
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 only (as a lipid emulsion). Propofol is not active orally (extensive first-pass metabolism) and is never taken by mouth clinically.. Propofol is a hospital anaesthetic, not a recreational drug, and the figures below are clinical reference doses for trained anaesthesia providers, not a guide to self-administration. It has an extremely narrow safety margin: hypnotic doses routinely cause apnoea and a fall in blood pressure, and it must be given only with full airway and resuscitation support. Non-medical use, including by healthcare workers with access, is frequently fatal, because the dose that produces anaesthesia and the dose that produces fatal respiratory arrest are very close and there is no reversal agent.

Dose ranges

Induction (adult)

1.5–2.5 mg/kg IV

Maintenance (infusion)

4–12 mg/kg/h IV

Procedural sedation

0.5–1 mg/kg IV, then titrated

Duration

onset

≈30–60 seconds (IV)

total

≈5–10 minutes after a single bolus (terminated by redistribution)

after effects

Rapid, usually clear recovery. Short-lived residual sedation and impairment

Chemical & Physical Properties
FormulaC12H18O
Molar mass178.27 g/mol
StateLiquid (oily, mp 18 °C)
Melting point18 °C
Boiling point256 °C
Density0.955 g/cm³ at 20 °C
Vapor pressureNot reported
pKa11.1 (20 °C)
LogP3.79
SolubilityPractically insoluble in water (~124–158 mg/L). Soluble in alcohol and toluene, Formulated for use as a 1% oil-in-water lipid emulsion
Refractive index1.5134 at 20 °C, 1.5111 at 25 °C
Identifiers & Synonyms
CAS2078-54-8
CAS (enantiomer)
PubChem CID4943
InChIKeyOLBCVFGFOZPWHH-UHFFFAOYSA-N
InChIInChI=1S/C12H18O/c1-8(2)10-6-5-7-11(9(3)4)12(10)13/h5-9,13H,1-4H3
SMILESCC(C)C1=C(C(=CC=C1)C(C)C)O

Synonyms

  • Diprivan
  • 2,6-diisopropylphenol
Pharmacodynamics & Biochemistry

Propofol (2,6-diisopropylphenol) is a short-acting intravenous general anaesthetic and sedative-hypnotic. It has no analgesic activity. Its actions are sedation, hypnosis and amnesia. Its principal molecular action is positive allosteric modulation of GABA-A receptors: at clinical concentrations it potentiates GABA-evoked chloride currents, and at higher concentrations it directly activates the receptor. This enhancement of inhibitory GABAergic transmission produces sedation, hypnosis and, at anaesthetic doses, unconsciousness. The hypnotic and immobilising actions depend particularly on GABA-A receptors containing the β3 subunit: a point mutation (N265M) in β3 strongly attenuates propofol's effects in vivo, identifying a transmembrane β-subunit site as the key locus of action. Propofol has weaker secondary actions at other channels. It blocks HCN1 channels, inhibits mechanosensitive TRPV4 and Piezo1/Piezo2 channels and some voltage-gated sodium channels, and modulates glycine receptors, but these occur mostly at higher, supra-clinical concentrations and are minor relative to its GABA-A action (which is why no binding table is shown: the databased quantitative values are only for these off-targets).

Biological targets

  • GABA-A
Pharmacokinetics
BioavailabilityIntravenous (100%), orally inactive (extensive first-pass metabolism)
TmaxEffect within ≈30–60 s of an IV bolus
Half-lifeRapid distribution (t½α ≈2–4 min), clinically short-acting by redistribution, with a long terminal half-life from deep (fat) compartments
VdNot reported
Protein binding≈97–99% (highly protein-bound and highly lipophilic)
MetabolismRapid hepatic and extrahepatic glucuronidation/hydroxylation (high clearance)
ExcretionRenal (inactive metabolites)
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

Propofol is one of the most widely used intravenous anaesthetics, but it is dangerous outside a controlled clinical setting. Hypnotic doses reliably cause respiratory depression and apnoea together with a drop in blood pressure, and there is no reversal agent: the margin between sedation and fatal respiratory arrest is small. Injection is often painful. Prolonged high-dose infusion can cause propofol infusion syndrome (PRIS): metabolic acidosis, rhabdomyolysis, hyperkalaemia and cardiac failure, which can be fatal and is a particular risk in children and the critically ill. Propofol also has genuine abuse potential: misuse for its rapid sedative, sleep-inducing and mildly euphoric effects, especially among anaesthesia and other healthcare workers with access, has caused numerous deaths, because self-administration without airway support readily proceeds to fatal apnoea.[3][6]

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

Opioids, Benzodiazepines, Alcohol Strongly additive sedation, respiratory depression and hypotension, so the propofol dose must be reduced when they are combined.[3]
General anaesthetics and other sedatives Other anaesthetics and sedatives lower the propofol dose required and deepen cardiorespiratory depression.[3]

Contraindications

Use outside monitored anaesthesia, without airway or resuscitation support for use only by personnel trained in general anaesthesia, with airway and resuscitation equipment available, as no reversal agent exists. Prolonged high-dose infusion also risks propofol infusion syndrome (PRIS), greatest in the critically ill and in children.[3]
Known hypersensitivity to the drug hypersensitivity to propofol or the emulsion (historically egg or soy lecithin).[6]
Cardiovascular disease, hypertension or arrhythmia haemodynamic instability, hypovolaemia or cardiorespiratory compromise (marked hypotension and apnoea).[3]
Usage & Context
  • A first-line intravenous agent for induction and maintenance of general anaesthesia, for procedural (conscious) sedation, and for sedation of ventilated patients in intensive care. Valued for its rapid onset and rapid, clear recovery.
  • Despite hospital-only availability it is misused for its rapid sedative and sleep-inducing effects, most notoriously among healthcare workers: a pattern associated with a high death rate because of the ease of fatal respiratory depression.
Sources & Evidence

Further Information