"Drugs which inhibit the breakdown of endogenous opioid peptides..."

[Lightning-Nl]

I happened to come across this study conducted in 2000 about the analgesic effects of Nitrous Oxide. The study measured the receptor affinity that N2O has for receptors in the body. They noted that N20 has mild opioid affinity. That alone I found interesting, however - to prove that this was the case, they pretreated the test animals with with a "Drugs which inhibit the breakdown of endogenous opioid peptides" and found that N20 had a much more powerful pain-killing effect when done so first.

Anyways, I started this thread because I wasn't aware of any drugs that could stop the reuptake of endogenous opioids. What's also interesting is the fact they hide the name of the first substances they used - only referring to them as "various inhibitors of peptidases." Doing a quick search on "inhibitor peptidases" gives for limited results for what the actual name of these chemicals are.

The other "reuptake inhibitor" is referred to as "Phosphoramidon." Again, after doing a quick search on this one, it turns back much more results - but the information about it is still limited. The only thing the Wikipedia article states is the fact that; such as grapefruit juice is an inhibitor of enzyme CYP3A4, phosphoramidon stops opioid peptides from being broken down by inhibiting the enzymes that are responsible for doing it.

From what I already know about endogenous opioids; they're secreted by the pituitary gland and therefore have an immediate and direct effect on the brain. I also know they're broken down almost immediately after they're released. So this leads me to assume that not only does phosphoramidon cross BBB (and therefore have a direct effect on the brain), but it must also inhibit all such enzymes around the body.

Anyways, this is entirely speculation and therefore isn't backed up by any medical proof, but rather my own prior knowledge. What is your guy's interpretation of this information?

I was unaware such chemicals existed until 10 minuets ago - did anyone else have any knowledge of these or their pharmacodynamics?

 

[Gaius]

I believe this was discussed before and, correct me if I'm wrong, the general conclusion was that 'opioid reuptake inhibitors' would generally have little value, as the concentrations of endogenous opioids they'd be working with are quite low. (This also seems to be why exogenous opioids are so potent)

Take this with a grain of salt though, I only skimmed the relevant discussions. I'd love to see something like this.

 

[treezy z]

dl-phenylalinine

 

[Epsilon Alpha]

I did a quick skim of the literature and found that most protease inhibitors used in this kind of research are very non-selective. This means that unless you specifically target a protease you're going to get some interesting side effects.

If you could do a search for the proteins responsible for the catabolism of endorphins you would have a more selective list of inhibitors. A pubmed review search should turn up that info relatively quickly.

 

[sekio]

dl-phenylalinine

never conclusively shown to be an enkephalinase

 

[gremlin moon]

After looking at the author bios, it seems that Raymond M Quock is the actual lead. I would email him -- after 20 years I am sure no one in his personal life can stand to hear another word about nitrous, mice and other drugs -- he will most likely be happy to have an interested party asking questions... His address and info is here: http://www.vetmed.wsu.edu/research_ipn/quock.aspx
A list of all of his research papers. http://www.researchgate.net/profile/Raymond_Quock/publications/
I bet the dude has a dedicated nitrous room in his house lol. He certainly "dabbles" in opiate, cannabinoid and tryptamine research and his main experiments seem to involve mice climbing stairs.