Just published this week. A non-opioid, NON sedating pain drug. Found solely my molecular modeling of the binding cleft in receptors related to the classic opioid receptors. THERE IS HOPE!!

https://medicalxpress.com/news/2022-09-non-opioid-compounds-squelch-pain-sedation.html

You can go ahead and be all responsible if you want,
but you missed out on a bunch of perfectly
good excuses :D


http://forums.pelicanparts.com/uploa...1664608898.jpg

Morphine after bypass surgery last year. I would drift in and out of reality but never had a sense of euphoria but I was also in shock dealing with what had just happened to my body.

I remember back in the early 90's my wife had a script for Demerol. I took one for sport. THAT was euphoric. Cleaned the whole house while happy as a clam. Never took another. That was it. I am glad that stuff is not laying around.

https://www.science.org/doi/10.1126/science.abn7065

Have a few thoughts on that article. Computational aspect imho is smoke n mirrors. Nothing really new out of that compared to a lot of known stuff. Especially when the main skeletons are relatively the same and only modifications of functional groups. Hence pro-drugs and isomers. What's interesting is the single bonds(spinning) with the ring. If i have some time I'll compile some known structures to outline the similarities.

Were you ever involved in combinatorial R&D? Man did we ever spin our wheels on that one.

My first wife was a prescription drug addict. Do I have stories…
I spent over $100,000 trying to help her find help. In the end I concluded she didn’t want help, but not until after she left.

My exposure to computational has been through a research setting using DFT on compounds already synthesized. Complete waste of time. But you need computational data to publish now…


I had lunch with a big opioid receptor phd/md researcher. They’re at the local va using their facilities for animal studies. Anyways. A lot of his work relied upon companies that can produce the desired compounds (which I’m sure you know, they cannot)… There’s a need for talented synthetic chemists.

There's at least a couple non-opioid pain drug candidates in development, one I looked at is Vertex VX548. Some reading I did suggested it might be somewhat comparable to Vicodin (hydrocodone). Drug discovery and development is incredibly hard and expensive, the drug could easily fail in clinical trials.

There will be a major commercial obstacle to any non-opioid pain drugs that are successfully developed, which is that opioids are effective and dirt cheap. It is not that "the pharma industry is making billions from opioids" - it was, but opioid pain drugs went off patent long ago - or that "the industry doesn't want an alternative" - only the generic drug companies (mostly Indian) might get hurt. But if you're Vertex, and VX548 succeeds, you'll be trying to sell a premium-priced non-opiod, and its not clear how much doctors, hospitals, insurers will cooperate, meanwhile your own patent life is ticking away, in several (5-8? don't recall patent expiry) years the generics will be making VX-548 and selling it cheaply.

I recently messaged my doctor asking for a Rx for oxycodone immediate release. Not oxymorphone, not hydrocodone, but specifically 15 mg oxycodone pills.

I knew this would raise his eyebrows, so I gave him the full explanation: a decade ago, I had a kidney stone, he Rx'd oxycodone 5 mg, I took one and it did its job and I put the bottle away. I eventually realized that the oxycodone also worked for gallstone attacks, and I started taking one each time one of those day-long-delights was starting. Eventually two were needed - shelf life is a thing I guess - and the gallstone attacks started becoming more frequent - from yearly-ish to every couple months now - but I still figured his original Rx would last until my gallbladder surgery which has taken forever to schedule (Covid, staffing shortages, surgeon's office). Well, doctor, I just had another gallstone attack that was the worst yet, and I used my last three original oxycodone pills - and my surgery is still two months away. I know lots of people undergoing joint replacement, and have tried what they get, and that's why I'm specifically asking for oxycodone, nothing else seems to work for me.

After a couple questions (15mg?) he sent a Rx for 5 mg tabs to my pharmacy. I was a little surprised, but pleased.

Soooooo the questions are which receptors in the brain that are responsible. Mu.kappa.delta. and other fundamental neuroscience questions.

Lsd works very well at relieving pain...