4 ms·

Not a primary source, but see slide 11 [0]. In this case, for the "10X" I think they're looking at the binding affinity to the u-receptor. Edit: realized that

by sndean 8y ago

Not a primary source, but see slide 11 [0]. In this case, for the "10X" I think they're looking at the binding affinity to the u-receptor. Edit: realized that doesn't answer your question about the relationship between binding affinity, relative effective dose in mg/kg, etc. At least when medicinal chemists I work with say "10X stronger" they're referring to the binding affinity. Not sure about what it means in a person. https://www.ctsi.ucla.edu/education/files/view/training/docs/FERRANTE_M263_Opioid_Pharmacology.pdf https://www.ctsi.ucla.edu/education/files/view/training/docs...

jessriedel 8y ago
Thanks! Though I'm willing to bet this technical parameter isn't what WaPo means by "powerful" :)
- dogma1138 8y ago
  I’m pretty sure it does the “potency” is derived by the Ki value of the opioid to the Mu receptor which is the affinity while they aren’t identical (the lower the Ki the higher the potency) they are interchangeable at these levels unless you are looking for much more complex pharmacology where agonism and multiple receptors come into play. Since pain relief opioids are full Mu receptor agonists the rest doesn’t really matter in the context of these articles this is accurate enough to be technically correct while not being generalized to all opioids such as low Ki opioids which are mixed agonists or antagonists which can be used to treat addiction and even overdose since they bind to they receptors but don't activate them fully or not at all which means that they block other opioids.
  - jessriedel 8y ago
    Sorry, I don't understand. Elsewhere you said > no at the “effective” dose it likely won’t matter the problem is that effective dose is irrelevant in this case because we are talking about substance abuse. Do you disagree with either of these? 1. In popular news coverage, or doctors talking with lay patients, the term "power" or "strength" of an opioid is shorthand for it's potency on normal (non-addicted) patients. That is, it is inversely related to the number of milligrams that must be administered to get effective pain relief for some fixed reference injury. 2. The potency of a drug is only weakly correlated with its potential for addiction. There are several opioids that are less potent than average but have a higher propensity for addiction than average, and vice versa.
    - dogma1138 8y ago
      Ok "affinity" it's how strongly it would bind to a receptor. Then there is agonism or antagonism which can be partial or full. Full agonism is the "strongest" activation that doesn't have anything to do with affinity because it just means it fully activates the receptor, the affinity is how likely it will be bound to the receptors. For opioids that are full agonists potency and affinity can be used essentially interchangeably these are all primary pain relief opioids and fully bind to the receptors in the same manner essentially, opioids which are mixed agonists or even antagonists such as those used to treat addiction or withdrawal can have very high affinity but low potency because while they bind to the receptor very strongly they don't fully activate it or even deactivate it but as their affinity is high they can beat other opioids to the binding and block the receptors. As this drug is a replacement for fentanyl it's a full agonist opioid which means that if it's more potent it has to have a lower Ki value which means higher affinity at a matching ratio.

by sndean 8y ago

jessriedel 8y ago

Thanks! Though I'm willing to bet this technical parameter isn't what WaPo means by "powerful" :)

dogma1138 8y ago
I’m pretty sure it does the “potency” is derived by the Ki value of the opioid to the Mu receptor which is the affinity while they aren’t identical (the lower the Ki the higher the potency) they are interchangeable at these levels unless you are looking for much more complex pharmacology where agonism and multiple receptors come into play. Since pain relief opioids are full Mu receptor agonists the rest doesn’t really matter in the context of these articles this is accurate enough to be technically correct while not being generalized to all opioids such as low Ki opioids which are mixed agonists or antagonists which can be used to treat addiction and even overdose since they bind to they receptors but don't activate them fully or not at all which means that they block other opioids.
- jessriedel 8y ago
  Sorry, I don't understand. Elsewhere you said > no at the “effective” dose it likely won’t matter the problem is that effective dose is irrelevant in this case because we are talking about substance abuse. Do you disagree with either of these? 1. In popular news coverage, or doctors talking with lay patients, the term "power" or "strength" of an opioid is shorthand for it's potency on normal (non-addicted) patients. That is, it is inversely related to the number of milligrams that must be administered to get effective pain relief for some fixed reference injury. 2. The potency of a drug is only weakly correlated with its potential for addiction. There are several opioids that are less potent than average but have a higher propensity for addiction than average, and vice versa.
  - dogma1138 8y ago
    Ok "affinity" it's how strongly it would bind to a receptor. Then there is agonism or antagonism which can be partial or full. Full agonism is the "strongest" activation that doesn't have anything to do with affinity because it just means it fully activates the receptor, the affinity is how likely it will be bound to the receptors. For opioids that are full agonists potency and affinity can be used essentially interchangeably these are all primary pain relief opioids and fully bind to the receptors in the same manner essentially, opioids which are mixed agonists or even antagonists such as those used to treat addiction or withdrawal can have very high affinity but low potency because while they bind to the receptor very strongly they don't fully activate it or even deactivate it but as their affinity is high they can beat other opioids to the binding and block the receptors. As this drug is a replacement for fentanyl it's a full agonist opioid which means that if it's more potent it has to have a lower Ki value which means higher affinity at a matching ratio.