N&PD Moderators: Skorpio
Novel Fentanyl Analogue
melange
Bluelighter
I am just talking about "feeling"
like I have only tried fent, and it feels so fake/lasts shortly
I feel the etorphine analogues would be more "pleasurable"
Sentience
Bluelighter
Totally agree with you on this one.
Super potency is a menace to the consumer. It just makes it harder to measure and easier to overdose on.
It's a menace to the community too. Some NY state cops were looking to talk to me a few years back after one of my friends OD'd cuz somebody dropped my name as a source. I got lucky cuz when he died I was interred in Illinois and couldn't possibly have been the source, but these days more and more when somebody drops dead, the cops come looking to pin a homicide charge on anyone who might've facilitated access to the chemical (even if you just help someone inject: true). And it's getting worse: Florida just approved the death penalty for methadone sourcing, so potentially if someone drinks your take-homes and punts the pail, it's your ass.
/navarone/
Bluelighter
Just think of all the pople who killed themselves with china white.
The average drug consumer is unfortunately way to naive and irresponsable.
Reason why so many designer drugs are now scheduled.
atara
Bluelighter
I believe it's called alpha-methylfentanyl.
melange
Bluelighter
one of the reasons I disliked Bill Clinton was because he was trying to get the death penalty approved for non violent crimes such as drug dealing
jesus christ people
has anyone heard of something called "personal responsibility"
Hammilton
Bluelighter
In line with what vecktor was saying...
a) this isn't novel by any means. A real novel fentanyl derivative? BDPC. It's not a fentanyl analogue but it could be said to have been derived from it (though I don't think this was actually or intentionally, the familial relationship can be seen).
b) smarter people than you have tried to come up with super new fentanyl derivatives. There is a wealth of data and papers dealing with these compounds. Read them all and then draw the compound that your research says should be the best one.
fencamfamine
Bluelighter
This is the win:
(by virtue of analogy to the stereoisomers of fluorohmfentanyl, 4 of which inactive; read the paper)
According to 'Current Medicinal Chemistry', placing a propane-1-one at the 4 position increases the potency of this series by around 20% - without adding isomers, of course. Since a 4-CN is one of the intermediates for carfentanil, one can easily see this introduction not being too complex.
Having said which, pure mu agonism isn't the way to make a 'nice' opioid. Delta agonism (C8813 for example) or DRI (tilidine) for examples, makes for a more euphoric compound. It's a pity that more work has not been done on those cyclohexanols. The fact that 2-thienyl>phenyl begs the question of the 2-furanyl...
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Fentanyl is not "overkill". Really you need ohmefentanyl to really get into the spirit of designer fentanyl analogues.
Here's a good free article I saw on pubmed:
http://www.ncbi.nlm.nih.gov/pubmed/12643347
Cell Res. 2003 Feb;13(1):29-34.
Ohmefentanyl stereoisomers induce changes of CREB phosphorylation in hippocampus of mice in conditioned place preference paradigm.
Gao C, Che LW, Chen J, Xu XJ, Chi ZQ.
fencamfamine
Bluelighter
Tachyphylaxis in action - nice. Another good reason why super-potent isn't super-good.
fencamfamine
Bluelighter
I think I have some research on DHE analogs with x30000 M potency (similar to the 4 propane-1-one OHMEfentanyl analogs). Another good way to die very quickly in the lab!
Any advance on x30000? ;-)
fencamfamine
Bluelighter
I seem to remember that some of the N-cyclopropylmethyl analogs (forget what's @ the 7 exactly) were much stronger analgesics. Not pure agonist, but very effective analgesia. Side-effects preclude usage. Super buprenorphine, I guess....
fencamfamine
Bluelighter
Re-reading the whole of this thread, it's odd nobody has mentioned MOR subtypes. Mu1 is where the bulk of analgesia lies (yes, delta is the other) but Mu2 is what leads to the respiratory depression (which is the usual cause of death in fentanyl overdose, I think). Fentanyl is good because it's more Mu1 selective than most classes of opioid. AMF (alpha methyl fentanyl) had a much lower LD50 because it had a lower Mu2 Ki.
I certainly agree that beyond a certain point, further potency is a BIG problem rather than an advantage, but at least people designing these things would attempt to design out Mu2 binding. It seems that the fentanyls that have been commercialized all have rather good Mu1/Mu2 binding ratios - those people think long & hard.
negrogesic
Bluelight Crew
Yes the fentanyls have a high therapeutic index and are widely used in anesthesia/perioperative medicine. But subjectively, the fentayl feels as though it is qualitatiely "missing something". It fails to have the euphoria of more pharmacologically complex opiods, and lacks" warmth". I would go for morphine over fentanyl, and even methadone or levorphanol over fentanyl.
fencamfamine
Bluelighter
I think the missing element may be kappa and delta activity. BDPC has delta activity but felt unlike M (according to the subject on this site) so all 3 may be needed. I noted that replacing the phenethyl of BDPC with a 2-thienylethyl increases potency by 20% or so. The 2-furanethyl may be quite a bit more potent.
I note other mixed mu/delta agonists are being developed. Some delta agonism seems to offset respiratory depression which is a good thing.
Interesting, but not something to play with, really.
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fencamfamine
Bluelighter
I looked at a few fentanyl-class drug patents. It seems the 2-furanylethyl analogs are roughly x3 the potency of the 2-thienylethyl counterparts (which are themselves roughly twice the potency of the phenethyl). This is exactly the same pattern as seen in the levorphanol derivatives.
I'm not looking at silly potency, I'm just wondering if there is another binding site inside the synaptic cleft that the N-phenethyl originally suggested.
The other thing I noted was that there is a tendency for a hydroxyl on beta carbon (relative to N) to increase potency - this is due to hydrogen bonding, apparently.
I just wonder if this means a simpler, medium potency compound has yet to be classified. I mean, I assume that's why tilidine & such are active at all.
