4 ms·

Ok, so I'm not a doctor or anyone with actual expertise in this area (I'm just a weirdo that reads way to much) and I am no way trying to challenge your expert

Ok, so I'm not a doctor or anyone with actual expertise in this area (I'm just a weirdo that reads way to much) and I am no way trying to challenge your expert opinion but I do have a question. Could the the result be attributed to something unique to loperamide's molecular structure versus traditional opioids? Again not an expert on this topic, but looking at the molecular structure of loperamide compared to organic derived opioids (opium, heroin, codeine, etc) or synthetic opioids like oxytocin, loperamide's molecular structure is markedly different. Could there be some other factor at play here?

wittyreference 6y ago
Challenge away, it's the internet! I think that it's possible but unlikely that loperamide is having a unique effect, because (a) they've shown that it's operating via the ATF4 mechanism, which is the same mechanism we see in other opioids (and multiple other drugs), and (b) loperamide's activity has generally been pretty well characterized and it doesn't really stand out (it's by no means a new drug - I remember taking it as a generic twenty years ago.) I'll admit it's possible in the broad sense because ATF4 isn't some super-specific pathway. It's a stress response signal. So while I think (b) above makes a unique mechanism unlikely, (a) by itself isn't a slam-dunk - there are a lot of stress signals that induce cell death when they get amped up enough, and can inhibit cell death if blocked off.
- dnautics 6y ago
  It could also be because they are seeing the ATF4 pathway light up (seaching for keys under the lamppost) and there's some side pathway that is molecule-specific, that is synergistic for the molecule's mechanism of action. just playing devil's advocate for the paper -- I happen to agree with witty's original comment thesis (except for the argument based on the authority of the journal it was published in)

wittyreference 6y ago

Challenge away, it's the internet! I think that it's possible but unlikely that loperamide is having a unique effect, because (a) they've shown that it's operating via the ATF4 mechanism, which is the same mechanism we see in other opioids (and multiple other drugs), and (b) loperamide's activity has generally been pretty well characterized and it doesn't really stand out (it's by no means a new drug - I remember taking it as a generic twenty years ago.) I'll admit it's possible in the broad sense because ATF4 isn't some super-specific pathway. It's a stress response signal. So while I think (b) above makes a unique mechanism unlikely, (a) by itself isn't a slam-dunk - there are a lot of stress signals that induce cell death when they get amped up enough, and can inhibit cell death if blocked off.

dnautics 6y ago
It could also be because they are seeing the ATF4 pathway light up (seaching for keys under the lamppost) and there's some side pathway that is molecule-specific, that is synergistic for the molecule's mechanism of action. just playing devil's advocate for the paper -- I happen to agree with witty's original comment thesis (except for the argument based on the authority of the journal it was published in)