There are a couple of interesting, but quite obscure and unassayed, opioids that are potent mu agonists and delta antagonists. Amazingly, this seems to prevent (or at least highly reduce) development of tolerance to at least the antinociceptive/pain-killing properties, which as far as I know is mediated through the same opioid receptor subtype (mu[1]) as the euphoria! I'm unable to find any research as to which degree this lack of tolerance development also applies to the euphoria (which isn't too surprising considering it's seen as an unwanted side effect of opioids...) but it definitely seems interesting.
Obviously there is going to be some development of tolerance to the euphoric qualities due to other feedback mechanisms (such as downregulation of the DAergic transmission in the nucleus accumbens), but this would probably be to a much lesser degree than the tolerance developed to normal opioids/opiates.
Most of these substances are peptides, but one interesting non-peptide one is 'SoRI 9409' (5'-(4-chlorophenyl)-17-(cyclopropylmethyl)-6,7-didehydro-3,14-dihydroxy-4,5alpha -epoxypyrido-[2',3':6,7]morphinan), which was first synthesized and assayed for opioid receptor affinity by Ananthan et al. (1999), and whose reduced antinociceptive tolerance development in vivo was confirmed by Wells et al. (2001).
Is anyone else as excited by these opioids as I am? We're talking legal, potent opioids which (possibly) doesn't cause much of a tolerance! Especially SoRI 9409 looks promising, as it seems to be possible to synthesize using a relatively simple route from commonly available and unwatched precursors - however, as it'd probably be against the forum rules, I won't go into the specifics here.
Maybe someone should synth. and bioassay various novel opioids (including SoRI 9409 and its' analogues) and make an OpioidsIHKAL
. It's somewhat unfortunate that most underground chemists/psychopharmacologists are so focused on entheogens, which I guess is the reason these opioids haven't received much - if any - attention from the community.
So - what do you guys think? Can these substances be expected to be enjoyable - and continue to be so without the steep increase in dosage normally needed with opioids if used regurlarly? Obviously I'm not expecting that one would be able to use them 24/7 and achieve a constant state of euphoria, but still...
References:
Ananthan S, et al. (1999) Synthesis, opioid receptor binding, and biological activities of naltrexone-derived pyrido- and pyrimidomorphinans. J Med Chem 42: 3527-3538
Wells JL, et al. (2001) In vivo pharmacological characterization of SoRI 9409, a nonpeptidic opioid mu-agonist/delta-antagonist that produces limited antinociceptive tolerance and attenuates morphine physical dependence. Pharmacol Exp Ther. 297:597-605.
Obviously there is going to be some development of tolerance to the euphoric qualities due to other feedback mechanisms (such as downregulation of the DAergic transmission in the nucleus accumbens), but this would probably be to a much lesser degree than the tolerance developed to normal opioids/opiates.
Most of these substances are peptides, but one interesting non-peptide one is 'SoRI 9409' (5'-(4-chlorophenyl)-17-(cyclopropylmethyl)-6,7-didehydro-3,14-dihydroxy-4,5alpha -epoxypyrido-[2',3':6,7]morphinan), which was first synthesized and assayed for opioid receptor affinity by Ananthan et al. (1999), and whose reduced antinociceptive tolerance development in vivo was confirmed by Wells et al. (2001).
Is anyone else as excited by these opioids as I am? We're talking legal, potent opioids which (possibly) doesn't cause much of a tolerance! Especially SoRI 9409 looks promising, as it seems to be possible to synthesize using a relatively simple route from commonly available and unwatched precursors - however, as it'd probably be against the forum rules, I won't go into the specifics here.
Maybe someone should synth. and bioassay various novel opioids (including SoRI 9409 and its' analogues) and make an OpioidsIHKAL
. It's somewhat unfortunate that most underground chemists/psychopharmacologists are so focused on entheogens, which I guess is the reason these opioids haven't received much - if any - attention from the community.So - what do you guys think? Can these substances be expected to be enjoyable - and continue to be so without the steep increase in dosage normally needed with opioids if used regurlarly? Obviously I'm not expecting that one would be able to use them 24/7 and achieve a constant state of euphoria, but still...
References:
Ananthan S, et al. (1999) Synthesis, opioid receptor binding, and biological activities of naltrexone-derived pyrido- and pyrimidomorphinans. J Med Chem 42: 3527-3538
Wells JL, et al. (2001) In vivo pharmacological characterization of SoRI 9409, a nonpeptidic opioid mu-agonist/delta-antagonist that produces limited antinociceptive tolerance and attenuates morphine physical dependence. Pharmacol Exp Ther. 297:597-605.
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But I'm not very familiar with any potential commercially availible starting materials (please PM me if you want, because I became rather curious). However I doubt anything like that is going to hit the market unless good starting materials (which narrow down the synthetic pathway drastically) really are availible or if the product is extremely potent. My guess is also that it probably is patented for the next 10 years or so which would prevent sales.
