Propofol
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Collated from TripSit, Pharmacology, DrugCentral, DailyMed. Where sources differ (e.g. dosing), Compare shows them side by side.
Also known as milk-of-amnesia, diprivanTS
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
Intravenous
Route dataTripSit
| Threshold | Light | Common | Strong | Heavy |
|---|---|---|---|---|
| — | 10–30 mg | 30–60 mg | 60–100 mg | —+ |
🧬 Receptor activityPHDC
| Target | Action | Affinity | Source | |
|---|---|---|---|---|
| 5-hydroxytryptamine receptor 2B | — | Ki 3499 nM | CHEMBL | Target5-hydroxytryptamine receptor 2B Action— AffinityKi 3499 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 2C | — | Ki 6051 nM | CHEMBL | Target5-hydroxytryptamine receptor 2C Action— AffinityKi 6051 nM SourceCHEMBL |
| Sodium-dependent noradrenaline transporter | — | Ki 9316 nM | CHEMBL | TargetSodium-dependent noradrenaline transporter Action— AffinityKi 9316 nM SourceCHEMBL |
| Carbonic anhydrase 2 | — | Ki 19500 nM | CHEMBL | TargetCarbonic anhydrase 2 Action— AffinityKi 19500 nM SourceCHEMBL |
| Unchecked | — | Ki 22994 nM | CHEMBL | TargetUnchecked Action— AffinityKi 22994 nM SourceCHEMBL |
| Carbonic anhydrase 1 | — | Ki 98900 nM | CHEMBL | TargetCarbonic anhydrase 1 Action— AffinityKi 98900 nM SourceCHEMBL |
| GABA A receptor alpha-2/beta-2/gamma-2 (GABRG2) | Positive allosteric modulator | 4.95 EC50 | DRUGCENTRAL | TargetGABA A receptor alpha-2/beta-2/gamma-2 (GABRG2) ActionPositive allosteric modulator Affinity4.95 EC50 SourceDRUGCENTRAL |
| GABA-A receptor alpha-1/beta-2/gamma-2 (GABRA1) | Positive allosteric modulator | 5.7 EC50 | DRUGCENTRAL | TargetGABA-A receptor alpha-1/beta-2/gamma-2 (GABRA1) ActionPositive allosteric modulator Affinity5.7 EC50 SourceDRUGCENTRAL |
| GABA-A receptor alpha-1/beta-3/gamma-2 (GABRA1) | Positive allosteric modulator | 5.39 EC50 | DRUGCENTRAL | TargetGABA-A receptor alpha-1/beta-3/gamma-2 (GABRA1) ActionPositive allosteric modulator Affinity5.39 EC50 SourceDRUGCENTRAL |
| Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 (Hcn1) | Blocker | 5.2 IC50 | DRUGCENTRAL | TargetPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 (Hcn1) ActionBlocker Affinity5.2 IC50 SourceDRUGCENTRAL |
| 5-hydroxytryptamine receptor 2B (HTR2B) | — | 5.456 Ki | DRUGCENTRAL | Target5-hydroxytryptamine receptor 2B (HTR2B) Action— Affinity5.456 Ki SourceDRUGCENTRAL |
| 5-hydroxytryptamine receptor 2C (HTR2C) | — | 5.218 Ki | DRUGCENTRAL | Target5-hydroxytryptamine receptor 2C (HTR2C) Action— Affinity5.218 Ki SourceDRUGCENTRAL |
| Arachidonate 15-lipoxygenase (ALOX15) | — | 5.119 IC50 | DRUGCENTRAL | TargetArachidonate 15-lipoxygenase (ALOX15) Action— Affinity5.119 IC50 SourceDRUGCENTRAL |
| Carbonic anhydrase 1 (CA1) | — | 4.71 IC50 | DRUGCENTRAL | TargetCarbonic anhydrase 1 (CA1) Action— Affinity4.71 IC50 SourceDRUGCENTRAL |
| Carbonic anhydrase 2 (CA2) | — | 4.005 IC50 | DRUGCENTRAL | TargetCarbonic anhydrase 2 (CA2) Action— Affinity4.005 IC50 SourceDRUGCENTRAL |
| Cytochrome P450 2C9 (CYP2C9) | — | 4.91 IC50 | DRUGCENTRAL | TargetCytochrome P450 2C9 (CYP2C9) Action— Affinity4.91 IC50 SourceDRUGCENTRAL |
| Fatty-acid amide hydrolase 1 (FAAH) | — | 4.284 IC50 | DRUGCENTRAL | TargetFatty-acid amide hydrolase 1 (FAAH) Action— Affinity4.284 IC50 SourceDRUGCENTRAL |
| GABA-A receptor; anion channel (Gabrp) | — | 5.4 IC50 | DRUGCENTRAL | TargetGABA-A receptor; anion channel (Gabrp) Action— Affinity5.4 IC50 SourceDRUGCENTRAL |
| Prostaglandin G/H synthase 1 (PTGS1) | — | 5.417 IC50 | DRUGCENTRAL | TargetProstaglandin G/H synthase 1 (PTGS1) Action— Affinity5.417 IC50 SourceDRUGCENTRAL |
| Sodium-dependent noradrenaline transporter (SLC6A2) | — | 5.031 Ki | DRUGCENTRAL | TargetSodium-dependent noradrenaline transporter (SLC6A2) Action— Affinity5.031 Ki SourceDRUGCENTRAL |
Mechanism of actionPHDM
The action of propofol involves a positive modulation of the inhibitory function of the neurotransmitter gama-aminobutyric acid (GABA) through GABA-A receptors.
PharmacodynamicsPHDM
Propofol is a sedative-hypnotic agent for use in the induction and maintenance of anesthesia or sedation. Intravenous injection of a therapeutic dose of propofol produces hypnosis rapidly with minimal excitation, usually within 40 seconds from the start of an injection (the time for one arm-brain circulation).
Pharmacokinetics
Half-lifePH
Initial distribution phase t<sub>1/2α</sub>=1.8-9.5 minutes. Second redistirubtion phase t<sub>1/2β</sub>=21-70 minutes. Terminal elimination phase t<sub>1/2γ</sub>=1.5-31 hours.
Terminal elimination half-life is 3 to 12 hours; prolonged administration may result in longer duration.
...The first-stage elimination half-life (t1/2 beta) of propofol /SRP: administered mixed with lidocaine/ in children was shorter (mean 9.3 +/- 3.8 (s.d.) min) than the values found in adults. This pharmacokinetic alteration may have clinical significance following repeated administration or continuous infusion of propofol.
An intravenous dose of 14C-propofol (0.47 mg/kg) /was/ administered to six male volunteers... . ...The half-lives of the first and second exponential phases, mean values 5 min and 97 min respectively, varied widely among subjects.
AbsorptionPHDM
Rapid - time to onset of unconsciousness is 15-30 seconds, due to rapid distribution from plasma to the CNS. Distribution is so rapid that peak plasma concentrations cannot be readily measured. Duration of action is 5-10 minutes.
It is chiefly eliminated by hepatic conjugation to inactive metabolites which are excreted by the kidney.
60 L/kg [healthy adults]
23 - 50 mL/kg/min
1.6 - 3.4 L/min [70 Kg adults]
The initial apparent volume of distribution is 13 to 76 L/kg.
MetabolismPH
Hepatically metabolized mainly by glucuronidation at the C1-hydroxyl. Hydroxylation of the benzene ring to 4-hydroxypropofol may also occur via CYP2B6 and 2C9 with subsequent conjugation to sulfuric and/or glucuronic acid. Hydroxypropofol has approximately 1/3 of hypnotic activity of propofol.
Hepatic; rapidly undergoes glucuronide conjugation to inactive metabolites. An unidentified route of extrahepatic metabolism may also exist, suggested by the fact that propofol clearance exceeds estimated hepatic blood flow.
To determine the cytochrome P450 (CYP) isoforms involved in the oxidation of propofol by human liver microsomes. The rate constant calculated from the disappearance of propofol in an incubation mixture with human liver microsomes and recombinant human CYP isoforms was used as a measure of the rate of metabolism of propofol. The correlation of these rate constants with rates of metabolism of CYP isoform-selective substrates by liver microsomes, the effect of CYP isoform-selective chemical inhibitors and monoclonal antibodies on propofol metabolism by liver microsomes, and its metabolism by recombinant human CYP isoforms were examined. The mean rate constant of propofol metabolism by liver microsomes obtained from 6 individuals was 4.2 (95% confidence intervals 2.7, 5.7) nmol/min/mg protein. The rate constants of propofol by microsomes were significantly correlated with S-mephenytoin N-demethylation, a marker of CYP2B6 (r=0.93, P<0.0001), but not with the metabolic activities of other CYP isoform-selective substrates. Of the chemical inhibitors of CYP isoforms tested, orphenadrine, a CYP2B6 inhibitor, reduced the rate constant of propofol by liver microsomes by 38% (P<0.05), while other CYP isoform-selective inhibitors had no effects. Of the recombinant CYP isoforms screened, CYP2B6 produced the highest rate constant for propofol metabolism (197 nmol/min/nmol P450). An antibody against CYP2B6 inhibited the disappearance of propofol in liver microsomes by 74% /and SRP: reduced in vitro metabolism by blocking CYP 2B6/. Antibodies raised against other CYP isoforms had no effect on the metabolism of propofol. CYP2B6 is predominantly involved in the oxidation of propofol by human liver microsomes.
Propofol has known human metabolites that include (2S,3S,4S,5R)-6-[2,6-Di(propan-2-yl)phenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid and 4-hydroxy-propofol.
Propofol is rapidly distributed into peripheral tissues after absorption. It is highly protein bound in vivo and is metabolised by conjugation in the liver. Propofol is metabolized mainly by glucuronidation by uridine diphosphate-glucuronosyltransferases (UGTs) and by hydroxylation by CYP2B6 and CYP2C enzymes. The enzymes SULT1A1 and NQO1 participate in later steps in propofol metabolism. An unidentified route of extrahepatic metabolism may also exist, suggested by the fact that propofol clearance exceeds estimated hepatic blood flow. (L1002, A600, A304). Propofol is hepatically metabolized mainly by glucuronidation at the C1-hydroxyl. Hydroxylation of the benzene ring to 4-hydroxypropofol may also occur via CYP2B6 and 2C9 with subsequent conjugation to sulfuric and/or glucuronic acid. Hydroxypropofol has approximately 1/3 of hypnotic activity of propofol.
Route of Elimination: It is chiefly eliminated by hepatic conjugation to inactive metabolites which are excreted by the kidney.
Half Life: Initial distribution phase t<sub>1/2α</sub>=1.8-9.5 minutes. Second redistirubtion phase t<sub>1/2β</sub>=21-70 minutes. Terminal elimination phase t<sub>1/2γ</sub>=1.5-31 hours.
Protein bindingPH
95 to 99%, primarily to serum albumin and hemoglobin
External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.