"Legal" RC synthetic opiods?

[JJ03]

I am curious to know if there are any RC opiod synthetics that may be available (not from someone on this forum). I searched for about an hour and I wasn't able to find a single one that was not strictly regarded as an analogue.

[dread]

Not to my knowledge.

[Hammilton]

yeah, I know that 3-nitromethopholine (3?) is available. At least it was. I think the proprietor may be in jail now though.

[daddysgone]

yeah, I know that 3-nitromethopholine (3?) is available. At least it was. I think the proprietor may be in jail now though.

Im confused. If this substance is legal, why is the proprietor in jail? Perhaps for unrelated reasons?

[fastandbulbous]

Hope none ever make it to the RC market as they are a disaster waiting to happen. Look at the irresponsible use of mephedrone etc, then translate that to legal RC opiates - many deaths will ensue

I've got loads of data on a myriad of opioids that'd be legal, but I'm fucked if I'm going to make them publically available as I feel it would just accelerate the likelyhood of RC opiates appearing on the RC market. I feel ba enough about the train wrecks that ensued from desoxy; I couldfn't live with the fallout of the same thing with opioids

[negrogesic]

There are couple legal opioids would could be potential RC's. Most vendors are however hesitant to sell RC opioids.

Bromadol is a legal, ultra-potent opioid, though I doubt its available as an RC:

[Hammilton]

Dirt cheap too.

I've published a list at opiophile.org about a year or so ago, but none of them have been made available as a result.

azaprocine, methopholine, bromadol, ciramadol, etc etc

lots available, but most have issues associated. huge potency, toxicity, partial agonists.

a full agonist without additional toxicity orally active at about 50mg would be perfect.

[fastandbulbous]

There are couple legal opioids would could be potential RC's. Most vendors are however hesitant to sell RC opioids.

Bromadol is a legal, ultra-potent opioid, though I doubt its available as an RC:

That's effectively a PCP derivative

[daddysgone]

Its been mentioned before, but the substance "dermorphin" which was isolated from the skin excretions of a certain species of frog, has been shown to be a potent mu opiate agonist.
I had a brief period where I became so interested in thsi substance, that I purchased a quantity of it online. While it does fulfill the requirement of "Legal synthetic opioid" that the OP is asking about, my experience with it was that it was not recreational in any way.
I made 2 attempts experimenting with dermporphin, both of which can be found in this thread
http://www.bluelight.ru/vb/showthrea...ght=dermorphin

I cant exactly explain why, but certain substances look good on paper, but fail to live up to the presumed, and desired effects. Dermorphin certainly APPEARS to be a potent mu agonist that should provide typical opioid effects, however in pratice, it fell quite short. It is entirely possible that my dissapointment in it was due to dosage errors (I was really just basically stabbing in the dark in terms of dosage since there is virtually no info out there on the effective human dosage). However, I DID experience effects from it, they were just in no way, pleasant. I found it far closer to dysphoric then euphoric.
Another problem with this particular class of drugs (opioid peptides), is that in almost all cases, they have an EXTREMELY short duration. Now, in the case of dermorphin, this turned out to be a plus since it was unpleasant, but if you were to find a recreational opioid peptide, chances are you would have to do some serious tweaking to this hypothetical molecule, in order to increase its duration.

Out of curiosity, has anyone else been brave or stupid enough to experiment with derpmorphin? Id love to hear if your experiences mirrored mine. Thanks-DG

[hamhurricane]

ive used p. bicolor skin secretions which contain dermorphin and many other related peptides. i rubbed the secretions into an open wound (in the amazon) and did not find it especially recreational, moderate euphoria, there are some ethnobotanical vendors which sell the secretions though.

[PsychedelicPeptide]

I have a feeling there are some "hidden gems" in the recent opioid peptide literature detailing analogs, or important information pertaining to making other analogs, that could allow one to have knowledge of a sequence and subsequent peptide that could be of recreational use.

Something like this:

Chem Biol Drug Des. 2009 Aug 20.
Cyclic Opioid Peptide Agonists and Antagonists Obtained Via Ring-Closing Metathesis.
Berezowska I, Lemieux C, Chung NN, Wilkes BC, Schiller PW.

Laboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, Canada H2W 1R7.

The opioid peptide H-Tyr-c[D-Cys-Phe-Phe-Cys]NH(2) cyclized via a methylene dithiother is a potent and selective mu opioid agonist (Przydial M.J. et al., J Peptide Res, 66, 2005, 255). Dicarba analogues of this peptide with Tyr, 2'6'-dimethyltyrosine (Dmt), 3-[2,6-dimethyl-4-hydroxyphenyl)propanoic acid (Dhp) or (2S)-2-methyl-3-(2,6-dimethyl-4-hydroxyphenyl)propanoic acid [(2S)-Mdp] in the 1-position were prepared. The peptides were synthesized on solid-phase by substituting d-allylglycine and (2S)-2-amino-5-hexenoic acid in position 2 and 5, respectively, followed by ring-closing metathesis. Mixtures of cis and trans isomers of the resulting olefinic peptides were obtained, and catalytic hydrogenation yielded the saturated -CH(2)-CH(2)- bridged peptides. All six Tyr(1)- and Dmt(1)-dicarba analogues retained high mu and delta opioid agonist potency and showed only slight or no preference for mu over delta receptors. As expected, the six Dhp(1)- and (2S)-Mdp(1)-dicarba analogues turned out to be mu opioid antagonists but, surprisingly, displayed a range of different efficacies (agonism, partial agonism or antagonism) at the delta receptor. The obtained results indicate that the mu versus delta receptor selectivity and the efficacy at the delta receptor of these cyclic peptides depend on distinct conformational characteristics of the 15-membered peptide ring structure, which may affect the spatial positioning of the exocyclic residue and of the Phe(3) and Phe(4) side chains.

--------------------------

J Med Chem. 2007 Jun 28;50(13):3138-42.
Synthesis of stable and potent delta/mu opioid peptides: analogues of H-Tyr-c[D-Cys-Gly-Phe-D-Cys]-OH by ring-closing metathesis.
Mollica A, Guardiani G, Davis P, Ma SW, Porreca F, Lai J, Mannina L, Sobolev AP, Hruby VJ.

Università degli Studi G. D' Annunzio, Via dei Vestini 31, I-66013 Chieti, Italy.

Ring-closing metathesis has emerged as a powerful tool in organic synthesis for generating cyclic structures via C-C double bond formation. Recently, it has been successfully used in peptide chemistry for obtaining cyclic molecules bridged through an olefin unit in place of the usual disulfide bond. Here, we describe this approach for obtaining cyclic olefin bridged analogues of H-Tyr-c[D-Cys-Gly-Phe-Cys]-OH. The synthesis of the new ligands was performed using the second generation Grubbs' catalyst. The resulting cis-8 (cDADAE) and trans-9 (tDADAE) were fully characterized and tested at delta, mu, and kappa opioid receptors. Also the linear precursor 13 (lDADAE) and the hydrogenated derivative 11 (rDADAE) also were tested. All the cyclic products containing a olefinic bond are slightly selective but highly active and potent for the delta and mu opioid receptors. Activity toward the kappa opioid receptors was absent or very low.

---------------------------------

J Med Chem. 2007 Jun 14;50(12):2779-86.
[b]Design, synthesis, and biological evaluation of novel bifunctional C-terminal-modified peptides for delta/mu opioid receptor agonists and neurokinin-1 receptor antagonists.[b/]
Yamamoto T, Nair P, Davis P, Ma SW, Navratilova E, Moye S, Tumati S, Lai J, Vanderah TW, Yamamura HI, Porreca F, Hruby VJ.

Department of Chemistry, University of Arizona, Tucson, Arizona 85721, USA.

A series of bifunctional peptides that act as agonists for delta and mu opioid receptors with delta selectivity and as antagonist for neurokinin-1 (NK1) receptors were designed and synthesized for potential application as analgesics in various pain states. The peptides were characterized using radioligand binding assays and functional assays using cell membrane and animal tissue. Optimization was performed on the fifth residue which serves as an address moiety for both receptor recognitions. It had critical effects on both activities at delta/mu opioid receptors and NK1 receptors. Among the synthesized peptides, H-Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-O-3,5-Bzl(CF3) 2 (5) and H-Tyr-D-Ala-Gly-Phe-Nle-Pro-Leu-Trp-O-3,5-Bzl(CF3)2 (7) had excellent agonist activity for both delta opioid and mu opioid receptors and excellent antagonist activity for NK1 receptors. These results indicate that the rational design of multifunctional ligands with opioid agonist and neurokinin-1 antagonist activities can be accomplished and may provide a new tool for treatment of chronic and several pain states.

-------->>> With regards to this last paper I saw a talk about this recently with a lot of in vivo data from mouse models and expect them to be doing some preclinical trials now or in the near future as the guy made it out to look like he had a "near ideal" pain-relieving compound that had no sign of behavioral effects or withdrawal/addiction. It almost sounded too good to be true. His explanation was in the fact that it had activity and the opioid receptor simultaneously with the NK1 antagonism, but that they couldn't fully prove it yet or something. Either way more information is bound to come up sooner or later.

[fastandbulbous]

If you really want to go down this route, but be safe, the best bet are to look at things like enkephalinase inhibitors like thiorphin. They prolong the activity of the body's endogenmous peptides of the enkephalin series (which I believe are the fun mu agonist ones). This presents much less chasnce of a fatal overdose, which is a fair probability with the ultra potent opioids

[daddysgone]

If you really want to go down this route, but be safe, the best bet are to look at things like enkephalinase inhibitors like thiorphin. They prolong the activity of the body's endogenmous peptides of the enkephalin series (which I believe are the fun mu agonist ones). This presents much less chasnce of a fatal overdose, which is a fair probability with the ultra potent opioids

That brings up an interesting question: If one were to take an effective enkephalinase inhibitor as you suggested, is it a possibility (however remote) that one could then overdose on one's own endogenous opioid peptides? Even if one could COMPLETELY achieve inhibition, I would doubt that your body could produce and accumulate a high enough concentration of opioid peptides to cause an overdose.....but then again. What do you think F&B

[amanitadine]

and f+b (hail mr. beefheart btw!), what role did you play in desoxys emergence? im *kinda* new here;D I feel you on the guilt anyhoo, well over a decade ago me and some bees from the old hive patched our proceeds together and hired a sweat shop chemist to make us some 2c-t-7, as this was sashas most interesting sounding creation that none of us had been successful at synthing, and this was well before it was really available...and sure as shit it was adored and spread like wildfire, virtually kicking of the RC market....and then dudes started dying. a few years later there was a bee reunion in the US federal penitentiary system and we got to wallow in our collective guilt for a few years....*sigh*

research opioids WILL be the death of the grey market, if it even lasts that long. It doesnt help that several chinese manufacturers are now selling explicitly scheduled compounds ( 2c-b, mescaline, etc) this will NOT last

[Hammilton]

That's effectively a PCP derivative

It is, but being that it's effects aren't similar to PCP, it's not an analogue.

There is a simplified analogue of bromadol, I forget the details exactly, that was closer to PCP, but was a pure mu agonist. details at blacklight, I remember.

[fastandbulbous]

and f+b (hail mr. beefheart btw!), what role did you play in desoxys emergence?

Have a look at trip reports - nobody had heard of the stuff when I made the original post that started the thread

[fastandbulbous]

That brings up an interesting question: If one were to take an effective enkephalinase inhibitor as you suggested, is it a possibility (however remote) that one could then overdose on one's own endogenous opioid peptides? Even if one could COMPLETELY achieve inhibition, I would doubt that your body could produce and accumulate a high enough concentration of opioid peptides to cause an overdose.....but then again. What do you think F&B

Don't know if an OD would be possible, but it'll be a sight safer than the ultra potent opioids people are talking about in this thread (and opioids are possibly the most diverse chemically of all the pharmacological groups of drugs of abuse, so there are 100s of possibilities)

[Hammilton]

I was thinking of 4-(dimethylamino)-4-phenylcyclohexanone, which isn't super potent by any means, but still a opioid and not a NMDA antagonist.

[fastandbulbous]

Strange, move the oxygen round two carbon atoms of te cyclohexane ring and you've got a ketamine analogue. Mu agonists, NMDA antagonists and DARIs have a huge overlapping range

[Hammilton]

Indeed. I believe it still has NMDA affinity, but it must be awfully low.

Murphy knows more.

[melange]

Man I hate that my pc broke - I jump into these awesome convos so late -everything has been said - the peptides are where it's at

[daddysgone]

I was thinking of 4-(dimethylamino)-4-phenylcyclohexanone, which isn't super potent by any means, but still a opioid and not a NMDA antagonist.

Hamm (or anyone else)-

what about 4-Cyano-4-phenylcyclohexanone
Would you expect to have mu opioid activity or be an NMDA antagonist (or both...or neither).

I initially thought this was just some sort of antifungal, but you mentioned 4-(dimethylamino)-4-phenylcyclohexanone so now I wonder

[fastandbulbous]

^ I'd expect it to be poisonous a la PCC

[daddysgone]

^^^^^^^^^^^^
Sure it'd be poisonous, but would it have have any opioid activity?

[dread]

Why does it matter?