Opioids Kappa antagonists

[crOOk]

Do you know of any kappa opioid receptor antagonists that have been used in human trials? I am interested in their potential to reduce compulsive drug seeking (or potentially other hedonistic types of) behaviour.

 

[brutus]

I honestly don't know so I did a Google scholar search. nor-binaltorphimine looks like it could be promising. Here's the link to Google and the source.

This may be better suited for ADD. I will move it there if you wish.

 

[cwake18]

Good question. I know bupe is a partial mu agonist and delta antagonist and nalbuphine is a kappa agonist while being a mu antagonist.

Pentazocine (Talwin) is a sigma and kappa agonist, and a weak mu antagonist. I would explore around these drugs and the agonist/antagonists as well as naloxone and naltrexone and similar drugs. As you may know, naltrexone is very checmically similar to oxymorphone (extremely potent my agonist) but naltrexone itself is an extremely powerful mu and kappa antagonist and exhibits kappa antogonism as well. Additionally you have nalorphine, another mu antag but kappa agonist

 

[sekio]

As far as I know, kappa opioid agonist are specifically avoided in medicine these days due to their propensity to cause hallucinations and dysphoria.

Usage of salvinorin is pretty "fringe" pharmacology, I think.

Is buprenorphine not a kappa agonist?

 

[crOOk]

As far as I know, kappa opioid antagonist are specifically avoided in medicine these days due to their propensity to cause hallucinations and dysphoria.

Usage of salvinorin is pretty "fringe" pharmacology, I think.

Is buprenorphine not a kappa agonist?

Those are kappa agonists you are thinking about. These are not of any interest, just like pentazocine.

Buprenorphine is an antagonist, but at the same time it is an agonist on other opioid receptors. I'm looking for a more selective substance for obvious reasons.

The same goes for naltrexone, it elicits very strong mu opioid antagonism which just isn't the idea. That would be hellish I'd assume even without currently using opiates.

@brutus
Thanks for the link, I will look into that! Might be better to move this to ADD, I considered posting it there anyway. Thank you!

 

[cwake18]

Do you know of any kappa opioid receptor antagonists that have been used in human trials? I am interested in their potential to reduce compulsive drug seeking (or potentially other hedonistic types of) behaviour.

Google "JDTic" it's very interesting. A kappa antagonist. Jdtic.com even. It's been mentioned on this forum. It's part of some new antidepressant/anxiolytic they're working on or something.

 

[crOOk]

Google "JDTic" it's very interesting. A kappa antagonist. Jdtic.com even. It's been mentioned on this forum. It's part of some new antidepressant/anxiolytic they're working on or something.

Wow that is exactly what I was looking for. You are THE MAN!
I'm just worries about trials being terminated for unknown reasons and the guy not posting on his own forum... Dead?

 

[cwake18]

Wikipedia claims that the trials were halted in 2012 due to ventricular tachycardia being experienced by some patients.

Yeah I'm not sure about it I haven't done a whole lot of research glad I could be of help

Also check out ALKS 5461 - it's a new drug being developed that uses buprenorphine essentially as an antidepressant/antianxiety and it's coupled with a drug called ALKS 33 that takes away the mu agonism of bupe and allows for it to be used for an antidepressant without abuse potential etc. Apparently, the kappa antagonism of it is what helps make it work so well, that's when I stumbled on jdtic.

 

[crOOk]

Yeah that's exactly why I'm thinking it might help me stop using (don't laugh) cannabis and actually find some enjoyment in studying again. I still wouldn't want a non selective antagonist like bup along with another med. Still gonna jump on the first kappa antagonist that's going into human trials.

 

[cwake18]

But that's the thing.

Bupe + ALKS 33 = ALKS 5461, a non-mu agonist, and a Kappa-Antagonist. This is what creates the antidepressant/anxiolytic effects. It's very similar to JDTic. Google ALKS 5461 then click the 6th link, should be a PDF file. It thoroughly explains ALKS 33 + BUPE, ALKS 5461, and how it works and what they're hoping to accomplish with ALKS 5461. It is a very nice PDF, fully color with nice information, graphs, and illustrations.

 

[crOOk]

But then I'll have my mu opioid receptors blocked, wtf. It doesn't sound too appealing. But then again, I'm getting on Lithium+SSRI, which isn't all that appealing either. Psychopharmaceuticals are FUCKING CRAP! Not that I'm not a big fan of the idea, but we haven't got SHIT so far. Useless fucking SSRI's, neuroleptics, antiepileptics and last but not least a fucking alkali metal as treatment options. That's how far 150 years of pharmaceutical developement have gotten us, fucking ridiculous.

Btw, wiki says "The first human trial of JDTic was halted abruptly in May 2012 due to instances of ventricular tachycardia experienced by participants". Awesome. Guess we know why this guy stopped posting lol.
http://clinicaltrials.gov/show/NCT01431586
http://www.mclean.harvard.edu/kappa.../Kappa-Therapeutics-2013-Complete-Program.pdf

 

[cwake18]

Yeah if you look at my post above, I edited it earlier to show that Wikipedia reference about why it was halted. Sucks, but whatever. Bupe and benzos for anxiety and depression

 

[adder]

Adding the selective mu antagonist is only because of the stigma put on drugs causing morphine-like euphoria, and I don't really think that the benefits of relieving depression with buprenorphine are less of an upside than the possibility of much lighter addiction caused by partial mu agonism is a downside. Buprenorphine pharmacokinetics make it suitable for tapering down and I can't see withdrawal from buprenorphine be more unpleasant than withdrawal from antidepressants used nowadays. I can't speak generally as I'm addicted to opioids and I use Suboxone as maintenance treatment, but I've suffered from depression all my teenage and adult life, and to me using buprenorphine for depression would be far from handing morphine. If that samidorphan-buprenorphine combo ever makes it to the market, it's going to be controlled in the same way buprenorphine formulations are. And perhaps they would be a need for more control, because I can see turning samidorphan to a potent mu agonist easy (4-OH seems to boost mu/kappa, delta ratio generally + that 6=O group is very fine, so...).

It's sadly all because of the stigmatization. Morphine-induced depression is because of its effects on kappa receptors and not mu receptors.