Citation noticeOur citation system is being overhauled
References and citation markers may currently be incomplete, mismatched, or incorrect. This system is being rebuilt and reviewed before the full site launch.
Propofol
Propofol is a potent intravenous anesthetic that rapidly induces sedation and unconsciousness1 and is used to begin and maintain general anesthesia.2 It was first synthesized in 1973 by John B. Glen. Recovery is generally rapid,3 with less frequent drowsiness, nausea, and vomiting than with some other anesthetics. Self-administration of propofol by health care professionals has been reported to result in fatalities and other injuries.2 Long-term use has also been reported to cause addiction.
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
These dosage ranges should be considered highly provisional. Propofol carries substantial risk when used outside controlled medical environments, and thorough research into its pharmacology and hazards is essential before any consideration of use.
Subjective Effects
Pharmacology
Pharmacodynamics
Propofol enhances GABA-A receptor activity through positive allosteric modulation, prolonging channel opening and strengthening inhibitory signaling. Its receptor interactions include potentiation of the β2 and β3 subunits; at high doses, it may also activate GABA-A receptors without GABA. Propofol inhibits fatty acid amide hydrolase, and reduced breakdown of anandamide may contribute to its sedative action through indirect CB1 receptor activation. Additional interactions include inhibition of sodium channels and activation of TRPA1 on sensory nerves.
Pharmacokinetics
Propofol rapidly distributes from plasma into the central nervous system and subsequently into peripheral tissues.4 Protein binding is 95-99%, primarily to albumin and hemoglobin, and its volume of distribution in healthy adults is 60 L/kg. Hepatic metabolism occurs mainly through glucuronidation of the C1 hydroxyl group, with additional ring hydroxylation by CYP2B6 and CYP2C9 followed by sulfate or glucuronide conjugation. It is also identified as a substrate of CYP2C8, CYP2C18, CYP2C19, UGT1A1, UGT1A6, and UGT1A9, an inhibitor of CYP1A2, CYP2E1, CYP3A and UGT1A1, a weak inhibitor of CYP3A4, and an inducer of P-glycoprotein. Elimination chiefly involves hepatic conjugation to inactive metabolites that are excreted by the kidneys.2 The initial distribution half-life is 1.8-9.5 minutes, the subsequent redistribution half-life is 21-70 minutes, and terminal elimination estimates range from 1.5-31 hours, with another reported estimate of 2-24 hours. Clearance is 23-50 mL/kg/min, equivalent to 1.6-3.4 L/min in 70 kg adults.2
Interactions
An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.
Tolerance
Harm Potential
Addiction & Dependence
Psychological
Propofol can be habit-forming, and addiction has been reported with long-term use.6
Toxicity
Self-administration of propofol by health care professionals has been reported to result in fatalities and other injuries.2 Multiple pediatric ICU deaths have been associated with propofol sedation.7
LD50 Data
| Species | Route | Value |
|---|---|---|
| Mouse | Intravenous | 53 mg/kg |
| Rat | Intravenous | 42 mg/kg |
| Mouse | Oral, in soybean oil | 1230 mg/kg |
| Rat | Oral, in soybean oil | 600 mg/kg |
Propofol frequently causes apnea and can substantially reduce respiratory rate, minute ventilation, tidal volume, mean inspiratory flow rate, and functional residual capacity.
Propofol can cause substantial hypotension, with reported blood pressure reductions of at least 30%, and can decrease systemic vascular resistance, myocardial blood flow, and myocardial oxygen consumption.
History & Culture
Discovery and development
John B. Glen, a British veterinary anesthesiologist and researcher at Imperial Chemical Industries (ICI), first synthesized propofol in 1973. Developed under the designation ICI 35868, it was selected through comparative studies of ortho-alkylated phenols. Glen received the 2018 Lasker-DeBakey…
Legality
International
Propofol has approved, investigational, and vet approved regulatory groupings.
By Country
United StatesPrescription only
CanadaPrescription only
TurkeyPrescription onlyReferences
Citations
Article Status
Step 1 · Automated synthesisAn autonomous workflow built by Josie Kins compiled this article's foundation from information published across the web.
- Step 2 · First-pass reviewPending
Not yet reviewed: this article is pending editorial review by Lyrea.
- Step 3 · Citation reviewPending
No one has reviewed this article's citations yet. That second pass checks each claim against the source it cites.
Suggest an edit
Spotted a mistake, an outdated claim, or something missing from the Propofol article? Send the editors a private note. Feedback lands in a moderation queue and is never shown on the site.
Wish to give generalised feedback? You can do so here.
