Will There Ever Be An SR-17018 for B3nz0s?

[bluemannn]

I know SR is a miracle drvg for 0p1ates,

but Will there ever be an "SR" for b3nz0s?
That would be a literal Godsend considering the h3ll that is b3nz0 WD.

Thx

 

[Shotta609]

I know SR is a miracle drvg for 0p1ates,

but Will there ever be an "SR" for b3nz0s?
That would be a literal Godsend considering the h3ll that is b3nz0 WD.

Thx

What exactly is that SR?

 

[Cleofus28]

What exactly is that SR?

Just google it. It’s a miracle and is about to be a banned substance. Even fir researchers

 

[TooTired]

I know SR is a miracle drvg for 0p1ates,

but Will there ever be an "SR" for b3nz0s?
That would be a literal Godsend considering the h3ll that is b3nz0 WD.

Thx

Hadn't thought about that but yes agreed.. BZ WD is the worst. something like that to reduce tolerance/help wd symptoms would be a godsend for real

But then "they" would probably end up scheduling it, just like the SR you're referring to

 

[privateprez]

Desalkylgidazepam (sorry if wrong spelling, from memory) is the closest to what you want, at least from what I've read online. It's also known as bromonordiazepam.

 

[baberuth]

I guess it depends on exactly what you mean by "an SR-17018 for benzos," but, in short, I'd guess no. I'm not a biochemist so don't quote me here, but this is why I say no:

The subjective effects of mu opioid agonists are sundry, and some of these effects are linked to different pathways of mu opioid agonism. SR-17018 preferentially stimulates G protein signaling pathways. (The mu opioid receptor is a G protein coupled receptor or GCPR.) In GCPRs, agonism induces a cascade of intracellular effects - essentially a growing chain reaction (more or less) that leads to the ultimate results you feel. What's different about SR-17018? It achieves what was just described while largely ignoring beta-arrestin recruitment. Beta-arrestin is involved in desensitization to GCPR agonism and receptor internalization, among other things. This is presumably why SR-17018 yields some opioid effects (namely analgesia) without others (notably euphoria and the accruing of tolerance, at least relative to traditional opioids).

The GABA A receptor that benzos bind is a ligand-gated ion channel, not a GCPR, so things just work differently. In my head at least, it's just a simpler system. Rather than having an extracellular ligand cause a growing cascade of intracellular effects which then interact with one another, mostly via positive feedback loops but in unique ways (as GCPRs do), a ligand-gated ion channel is basically just a pore that opens to permit something to enter or exit the cell when bound by a ligand. Now once again, things can happen inside the cell that make it more complicated than that, but that's more of an afterthought for ligand-gated ion channels while, for GCPRs, it's the whole point of agonism.

Maybe worth mentioning that benzos are NOT the endogenous ligand at GABA A (probably obvious). That would be GABA, which shocker. Benzos bind allosterically, meaning at a separate site than the "usual" endogenous ligand, and then, once GABA (the neurotransmitter, not the receptor) comes along, the GABA A receptor will respond differently to GABA binding it when benzos are present than when they are not. So maybe a better understanding of allosteric modulation at GABA A could help us pare down the negative effects of benzos while retaining the positives, but as far as creating a drug that achieves what benzos do without accruing significant tolerance... I do not see how that would work. But I could be wrong!

 

[privateprez]

Ver

I guess it depends on exactly what you mean by "an SR-17018 for benzos," but, in short, I'd guess no. I'm not a biochemist so don't quote me here, but this is why I say no:

The subjective effects of mu opioid agonists are sundry, and some of these effects are linked to different pathways of mu opioid agonism. SR-17018 preferentially stimulates G protein signaling pathways. (The mu opioid receptor is a G protein coupled receptor or GCPR.) In GCPRs, agonism induces a cascade of intracellular effects - essentially a growing chain reaction (more or less) that leads to the ultimate results you feel. What's different about SR-17018? It achieves what was just described while largely ignoring beta-arrestin recruitment. Beta-arrestin is involved in desensitization to GCPR agonism and receptor internalization, among other things. This is presumably why SR-17018 yields some opioid effects (namely analgesia) without others (notably euphoria and the accruing of tolerance, at least relative to traditional opioids).

The GABA A receptor that benzos bind is a ligand-gated ion channel, not a GCPR, so things just work differently. In my head at least, it's just a simpler system. Rather than having an extracellular ligand cause a growing cascade of intracellular effects which then interact with one another, mostly via positive feedback loops but in unique ways (as GCPRs do), a ligand-gated ion channel is basically just a pore that opens to permit something to enter or exit the cell when bound by a ligand. Now once again, things can happen inside the cell that make it more complicated than that, but that's more of an afterthought for ligand-gated ion channels while, for GCPRs, it's the whole point of agonism.

Maybe worth mentioning that benzos are NOT the endogenous ligand at GABA A (probably obvious). That would be GABA, which shocker. Benzos bind allosterically, meaning at a separate site than the "usual" endogenous ligand, and then, once GABA (the neurotransmitter, not the receptor) comes along, the GABA A receptor will respond differently to GABA binding it when benzos are present than when they are not. So maybe a better understanding of allosteric modulation at GABA A could help us pare down the negative effects of benzos while retaining the positives, but as far as creating a drug that achieves what benzos do without accruing significant tolerance... I do not see how that would work. But I could be wrong!

Very detailed, thorough answer. Thanks for putting the effort in to give us all some insight.

 

[Cal1lab]

I guess it depends on exactly what you mean by "an SR-17018 for benzos," but, in short, I'd guess no. I'm not a biochemist so don't quote me here, but this is why I say no:

The subjective effects of mu opioid agonists are sundry, and some of these effects are linked to different pathways of mu opioid agonism. SR-17018 preferentially stimulates G protein signaling pathways. (The mu opioid receptor is a G protein coupled receptor or GCPR.) In GCPRs, agonism induces a cascade of intracellular effects - essentially a growing chain reaction (more or less) that leads to the ultimate results you feel. What's different about SR-17018? It achieves what was just described while largely ignoring beta-arrestin recruitment. Beta-arrestin is involved in desensitization to GCPR agonism and receptor internalization, among other things. This is presumably why SR-17018 yields some opioid effects (namely analgesia) without others (notably euphoria and the accruing of tolerance, at least relative to traditional opioids).

The GABA A receptor that benzos bind is a ligand-gated ion channel, not a GCPR, so things just work differently. In my head at least, it's just a simpler system. Rather than having an extracellular ligand cause a growing cascade of intracellular effects which then interact with one another, mostly via positive feedback loops but in unique ways (as GCPRs do), a ligand-gated ion channel is basically just a pore that opens to permit something to enter or exit the cell when bound by a ligand. Now once again, things can happen inside the cell that make it more complicated than that, but that's more of an afterthought for ligand-gated ion channels while, for GCPRs, it's the whole point of agonism.

Maybe worth mentioning that benzos are NOT the endogenous ligand at GABA A (probably obvious). That would be GABA, which shocker. Benzos bind allosterically, meaning at a separate site than the "usual" endogenous ligand, and then, once GABA (the neurotransmitter, not the receptor) comes along, the GABA A receptor will respond differently to GABA binding it when benzos are present than when they are not. So maybe a better understanding of allosteric modulation at GABA A could help us pare down the negative effects of benzos while retaining the positives, but as far as creating a drug that achieves what benzos do without accruing significant tolerance... I do not see how that would work. But I could be wrong!

You know more about drugs than me and that doesn’t happen often

 

[baberuth]

You know more about drugs than me and that doesn’t happen often

Hahaha I do love drug science but I have a career that probably gives me a bit of a cheat code in that regards.

 

[Layne_Cobain]

I wish. Been on benzos daily for 15ish years and my brain is fried and my anxiety n panic 1,000,000X worse. I thought I remember reading that flumazenil, the drug used to reverse benzo OD, had potential and had even shown to help with rapid benzo detox but idk if that was more for ppl abusing benzos for a shorter amount of time then ppl on them chronically