2-Minute Neuroscience: Fentanyl

Fentanyl is a highly potent opioid drug that’s approximately 75-100 times more potent than morphine, and has a rapid time to onset compared to many other opioids. This combination of high potency and rapid onset make fentanyl more likely to cause serious and potentially fatal reactions. In this video, I discuss the mechanism of fentanyl and what makes it different from other opioid drugs.

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TRANSCRIPT
Fentanyl is a highly potent opioid drug that’s approximately 75-100 times more potent than morphine, and has a rapid time to onset compared to many other opioids. This combination of high potency and rapid onset make fentanyl more likely to cause serious and potentially fatal reactions. Additionally, because fentanyl is often mixed with or substituted for other drugs sold on the street, it can be sold to unsuspecting users who might unintentionally administer a dangerous dose of the drug.

Fentanyl’s general mechanism of action is similar to other opioid drugs: It binds to receptors called opioid receptors, showing its highest affinity or attraction for a subtype of opioid receptor called a mu-opioid receptor. Fentanyl activates mu-opioid receptors, but the activation of these receptors typically leads to inhibition of the neuron they are present on. This inhibition can cause a reduction in pain signaling as well as the other effects of opioids, which range from sedation to the inhibition of respiratory function at high doses.

Fentanyl does not appear to display a stronger affinity for opioid receptors than other opioids like morphine do, so factors besides receptor affinity must be able to explain its higher potency. Although all of the reasons for fentanyl’s higher potency are not yet clear, one important factor may be its high lipid solubility. Due to this high lipid solubility, fentanyl can more quickly pass into the nervous system, and it may also be able to slightly penetrate the cell membrane to position itself closer to opioid receptors in order to interact with them. Fentanyl has also been found to be less sensitive to the effects of naloxone, or Narcan, a drug that can be used to reverse an opioid overdose. The reasons for this are not yet clear, but it is an area of active research.

REFERENCES

Burns SM, Cunningham CW, Mercer SL. DARK Classics in Chemical Neuroscience: Fentanyl. ACS Chem Neurosci. 2018 Oct 17;9(10):2428-2437. doi: 10.1021/acschemneuro.8b00174. Epub 2018 Jun 12. PMID: 29894151.

Comer SD, Cahill CM. Fentanyl: Receptor pharmacology, abuse potential, and implications for treatment. Neurosci Biobehav Rev. 2019 Nov;106:49-57. doi: 10.1016/j.neubiorev.2018.12.005. Epub 2018 Dec 5. PMID: 30528374; PMCID: PMC7233332.

Corder G, Castro DC, Bruchas MR, Scherrer G. Endogenous and Exogenous Opioids in Pain. Annu Rev Neurosci. 2018 Jul 8;41:453-473. doi: 10.1146/annurev-neuro-080317-061522. Epub 2018 May 31. PMID: 29852083; PMCID: PMC6428583.

Kelly E, Sutcliffe K, Cavallo D, Ramos-Gonzalez N, Alhosan N, Henderson G. The anomalous pharmacology of fentanyl. Br J Pharmacol. 2023 Apr;180(7):797-812. doi: 10.1111/bph.15573. Epub 2021 Jul 2. PMID: 34030211.
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Видео 2-Minute Neuroscience: Fentanyl канала Neuroscientifically Challenged