pti609 A non-addictive opioid

[serotonin2A]

It is undoubtedly in one of the patents. The problem is figuring out which compound it is. You might be able to figure it out by the process of elimination.

 

[palmanita]

Nagelfar, also had to think about DAMGO when reading the title wonder why this isn't researched further, or derivates of it.

Well, it's highly interesting that (if I understand it correctly) the most relevant binding site of naloxone/naltrexone is different from mu/delta/kappa and this (pentapeptide region on FLNA) is combined here with mu agonist activity.

Would administering pti-609 to opioid dependent people/animals cause a precipitated withdrawal, and what if one waits long enough before, like when switching to buprenorphine? If not, this could prove ideal to taper off opioids ...

But of course the possible place aversion is relevant. For me the graph already looks like place aversion, both tested dosages went below vehicle, it's just one test though.

I got accidentally exposed to a tiny dosage of naloxone nasally (1.5mg maybe), when I wasn't opioid dependent but took a high dose of 40mg/d of memantine. This was an hour of pure, distilled anxiety, depression and sad/hopelessness. Never ever felt so lonely and cold in my life. No physical symptoms because I wasn't dependent, no physical pain either, so I wonder very much about what it actually did. The inverse agonism of mu might be dysphoric by itself, also the displace of endorphins, but the alcoholics seem not to feel much from taking a huge 50mg naltrexone ... so it must have to do with the memantine, probably with instantly shutting the D2 agonism off (I had withdrawal from memantine later too, which surprised me and it wasn't easy, not comparable to naloxone by any means though.)

If pti-609 is devoid of reward or even downright dysphoric as naloxone, then I'd imagine it might be the neuroleptic of opioids- something nobody would take unless he's in strong pain (and in such a condition there are probably already a lot of endorphins at work, and it could be strongly dysphoric too)?

Maybe we'll find out sooner or later by RC people doing the human testing for them

On the other side, by doing the inverse of the non-mu side of naloxone, maybe one could create a non-opioid euphorisant lacking the physical side of opioids, or?

(Just my thinking - it is possible to take the withdrawal and even tolerance development off opioids to some extent [show memantine or dextromethorphan studies for combined pain treatment etc] but relief of pain always raises the level of confidence because everyone of us has some minor or major worries, pains etc. at any point of our life. Only strictly pheriperally acting things like topical local anesthetics lack physical effects. Even paracetamol gets abused..)

 

[polymath]

Combined mu agonist/delta antagonists are another class of compounds that are thought to produce analgesia without development of tolerance and dependence. Delta receptor blockage also seems to reduce cocaine self-administration. There seem to be many ways to slow down opioid tolerance development but none of them have been approved for real medical use, for whatever reason..

 

[serotonin2A]

But of course the possible place aversion is relevant. For me the graph already looks like place aversion, both tested dosages went below vehicle

The error bars are very wide. The graphs are a bit misleading because the y-axis is truncated (it doesn't start at 0), which tends to make marginal effects appear larger.