Propofol

Effects

Overview

A very short acting sedative that is usually given at the start of general anesthesia, and for maintenance of the prior. It should never be used outside of a medical setting. With that in mind, if you do plan to use this drug recreational, please have a very experienced friend with you that has the skills to insert a cannula, and monitor you very closely. TS

Propofol is the active component of an intravenous anesthetic used for induction and maintenance of general anesthesia. Propofol was first marketed under the brand name Diprivan. Intravenous administration is used to induce unconsciousness, after which anesthesia may be maintained using a combination of medications. Propofol is manufactured as part of a sterile injectable emulsion using soybean oil and lecithin, which gives it a white milky color.[1][2] WP

Compared to other anesthetics, recovery from propofol-induced anesthesia is generally quick and infrequently associated with such side effects as drowsiness, nausea, vomiting. Propofol may be used before diagnostic procedures requiring anesthesia, in the management of refractory status epilepticus, and for induction or maintenance of anesthesia before and during surgery. It may be administered as a bolus or an infusion, or as a combination of the two.[3][4] WP

First synthesized in 1973 by John B. Glen, a British veterinary anesthesiologist working for Imperial Chemical Industries (ICI, later AstraZeneca), propofol was introduced for therapeutic use as a lipid emulsion in the United Kingdom and New Zealand in 1986. Propofol (Diprivan) received FDA approval in October 1989. It is on the World Health Organization's List of Essential Medicines.[5][6] WP

History

History

John B. Glen, a veterinarian and researcher at Imperial Chemical Industries (ICI), spent thirteen years developing propofol, an effort for which he was awarded the 2018 Lasker Award for clinical research. WP

Originally developed as ICI 35868, propofol was chosen after extensive evaluation and structure–activity relationship studies of the anesthetic potencies and pharmacokinetic profiles of a series of ortho-alkylated phenols.[7] WP

First identified as a drug candidate in 1973, propofol entered clinical trials in 1977, using a form solubilized in cremophor EL. However, due to anaphylactic reactions to cremophor, this formulation was withdrawn from the market and subsequently reformulated as an emulsion of a soya oil and propofol mixture in water. The emulsified formulation was relaunched in 1986 by ICI (whose pharmaceutical division later became a constituent of AstraZeneca) under the brand name Diprivan. The preparation contains 1% propofol, 10% soybean oil, and 1.2% purified egg phospholipid as an emulsifier, with 2.25% glycerol as a tonicity-adjusting agent, and sodium hydroxide to adjust the pH. Diprivan contains EDTA, a common chelation agent that also acts alone (bacteriostatically against some bacteria) and synergistically with some other antimicrobial agents. Newer generic formulations contain sodium metabisulfite as an antioxidant and benzyl alcohol as an antimicrobial agent. Propofol emulsion is an opaque white fluid due to the scattering of light from the emulsified micelle formulation.[8] WP

Legal status

Pharmacology

Pharmacodynamics

Propofol's proposed mechanism of actionsuggests potentiation of GABAA receptor activity by acting as a GABAA receptor positive allosteric modulator, which slows receptor channel-closing time. At high doses, propofol may activate GABAA receptors in the absence of GABA, behaving as a GABAA receptor agonist as well. Propofol analogs also seem to act as sodium channel blockers.[9–16] WP

Some research suggested significant endocannabinoid system contributions to propofol's unique anesthetic properties, as endocannabinoids also play an important role in the physiologic control of sleep, pain processing and emesis. An EEG study on patients undergoing general anesthesia with propofol found that it causes a prominent reduction in the brain's information integration capacity. A 2026 study using Neuropixels detected hippocampus activity distinguishing sounds and recognizing language under general anesthesia with propofol.[17–20] WP

Propofol inhibits fatty acid amide hydrolase, which metabolizes the endocannabinoid anandamide (AEA). Activation of the endocannabinoid system by propofol, possibly via inhibition of AEA catabolism, generates a significant increase in the whole-brain content of AEA, contributing to the sedative properties of propofol via CB1 receptor activation. This may explain the psychotomimetic and antiemetic properties of propofol. By contrast, there is a high incidence of postoperative nausea and vomiting after administration of volatile anesthetics, which contribute to a significant decrease in the whole-brain content of AEA that can last up to forty minutes after induction.[18][21] WP

Pharmacokinetics

Propofol is highly protein-bound in vivo and is metabolized by conjugation in the liver. The half-life of elimination of propofol has been estimated to be between 2 and 24 hours. However, its duration of clinical effect is much shorter because propofol is rapidly distributed into peripheral tissues. When used for IV sedation, a single dose of propofol typically wears off within minutes. Onset is rapid, in as little as 15–30 seconds. Propofol's versatility allows it to be used for short or prolonged sedation, and general anesthesia; and unlike opioid medications, its use is not associated with nausea. These characteristics of rapid onset and recovery along with its amnestic effects have led to its widespread use for sedation and anesthesia.[22][23][24] WP

Chemistry

Formula

C12H18O PC

CAS number

2078-54-8 PC

Molar mass (g/mol)

178.27 PC

IUPAC name (computed by PubChem)

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

SMILES

CC(C)C1=C(C(=CC=C1)C(C)C)O PC

InChIKey

OLBCVFGFOZPWHH-UHFFFAOYSA-N PC

PubChem CID

4943

Pop culture

No references added yet.

References

1. Journal / agency Propofol
2. Other Making Stable, Sterile Propofol
3. Harm reduction site Propofol
4. Journal / agency Glen JB. The Discovery and Development of Propofol Anesthesia: The 2018 Lasker-DeBakey Clinical Medical Research Award. JAMA. September 2018. doi:10.1001/jama.2018.12756 · PMID 30208399
5. Journal / agency Glen JB. Try, try, and try again: personal reflections on the development of propofol. British Journal of Anaesthesia. July 2019. doi:10.1016/j.bja.2019.02.031 · PMID 30982566
6. Other World Health Organization model list of essential medicines: 22nd list (2021). 2021
7. Journal / agency James R, Glen JB. Synthesis, biological evaluation, and preliminary structure-activity considerations of a series of alkylphenols as intravenous anesthetic agents. Journal of Medicinal Chemistry. December 1980. doi:10.1021/jm00186a013 · PMID 7452689
8. Other Lasker Foundation. Discovery and development of propofol, a widely used anesthetic
9. Journal / agency Trapani G, Altomare C, Liso G, Sanna E, Biggio G. Propofol in anesthesia. Mechanism of action, structure-activity relationships, and drug delivery. Current Medicinal Chemistry. February 2000. doi:10.2174/0929867003375335 · PMID 10637364
10. Journal / agency Kotani Y, Shimazawa M, Yoshimura S, Iwama T, Hara H. The experimental and clinical pharmacology of propofol, an anesthetic agent with neuroprotective properties. CNS Neuroscience & Therapeutics. Summer 2008. doi:10.1111/j.1527-3458.2008.00043.x · PMID 18482023 · PMC6494023
11. Journal / agency Vanlersberghe C, Camu F. Modern Anesthetics. 2008. doi:10.1007/978-3-540-74806-9_11 · PMID 18175094
12. Journal / agency Trapani G, Latrofa A, Franco M, Altomare C, Sanna E, Usala M, Biggio G, Liso G. Propofol analogues. Synthesis, relationships between structure and affinity at GABAA receptor in rat brain, and differential electrophysiological profile at recombinant human GABAA receptors. Journal of Medicinal Chemistry. May 1998. doi:10.1021/jm970681h · PMID 9599235
13. Journal / agency Krasowski MD, Jenkins A, Flood P, Kung AY, Hopfinger AJ, Harrison NL. General anesthetic potencies of a series of propofol analogs correlate with potency for potentiation of gamma-aminobutyric acid (GABA) current at the GABA(A) receptor but not with lipid solubility. The Journal of Pharmacology and Experimental Therapeutics. April 2001. doi:10.1016/S0022-3565(24)29544-6 · PMID 11259561
14. Journal / agency Krasowski MD, Hong X, Hopfinger AJ, Harrison NL. 4D-QSAR analysis of a set of propofol analogues: mapping binding sites for an anesthetic phenol on the GABA(A) receptor. Journal of Medicinal Chemistry. July 2002. doi:10.1021/jm010461a · PMID 12109905 · PMC2864546
15. Journal / agency Haeseler G, Leuwer M. High-affinity block of voltage-operated rat IIA neuronal sodium channels by 2,6 di-tert-butylphenol, a propofol analogue. European Journal of Anaesthesiology. March 2003. doi:10.1017/s0265021503000371 · PMID 12650493
16. Journal / agency Haeseler G, Karst M, Foadi N, Gudehus S, Roeder A, Hecker H, Dengler R, Leuwer M. High-affinity blockade of voltage-operated skeletal muscle and neuronal sodium channels by halogenated propofol analogues. British Journal of Pharmacology. September 2008. doi:10.1038/bjp.2008.255 · PMID 18574460 · PMC2538694
17. Journal / agency Fowler CJ. Possible involvement of the endocannabinoid system in the actions of three clinically used drugs. Trends in Pharmacological Sciences. February 2004. doi:10.1016/j.tips.2003.12.001 · PMID 15106622
18. Journal / agency Schelling G. Effects of General Anesthesia on Anandamide Blood Levels in Humans. Anesthesiology. 2006. doi:10.1097/00000542-200602000-00012 · PMID 16436846
19. Journal / agency Lee U, Mashour GA, Kim S, Noh GJ, Choi BM. Propofol induction reduces the capacity for neural information integration: implications for the mechanism of consciousness and general anesthesia. Consciousness and Cognition. March 2009. doi:10.1016/j.concog.2008.10.005 · PMID 19054696
20. Other Krywko, Jacek. The brain processes overheard words under anesthesia, but it may not remember them. May 6, 2026
21. Journal / agency Patel S, Wohlfeil ER, Rademacher DJ, Carrier EJ, Perry LJ, Kundu A, Falck JR, Nithipatikom K, Campbell WB, Hillard CJ. The general anesthetic propofol increases brain N-arachidonylethanolamine (anandamide) content and inhibits fatty acid amide hydrolase. British Journal of Pharmacology. July 2003. doi:10.1038/sj.bjp.0705334 · PMID 12839875 · PMC1573928
22. Journal / agency Favetta P, Degoute CS, Perdrix JP, Dufresne C, Boulieu R, Guitton J. Propofol metabolites in man following propofol induction and maintenance. British Journal of Anaesthesia. May 2002. doi:10.1093/bja/88.5.653 · PMID 12067002
23. Other Propofol
24. Journal / agency Veselis RA, Reinsel RA, Feshchenko VA, Wroński M. The comparative amnestic effects of midazolam, propofol, thiopental, and fentanyl at equisedative concentrations. Anesthesiology. October 1997. doi:10.1097/00000542-199710000-00007 · PMID 9357875

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