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Faxeladol

Reminisant B

Reminisant B

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Joined
Nov 3, 2005
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401
Interesting derivative of tramadol. Demethyl-desoxy-tramadol if I have got that right.

Faxeladol

http://en.wikipedia.org/wiki/Faxeladol

Couldn't find any pubmed articles on it, althought would guess the demethyl increase potency but desoxy reduces [?]
 

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it'd be interesting to know more about the structure activity relationships of these tramadol-type MORAs.

aren't the more potent tramadol-analogues monocyclic, like tapentadol?
 
I would like to know if all drugs of this class carry the same risk of seizures. Also, do the NARI effects really contribute to the analgesia, or is it just a marketing ploy?
 
I think it's a side effect more than anything. They can't get a pure opioid effect (AFAIK) from these compounds, so run with it.

that and NARIs will decrease the sedation.
 
NARI and analgesia:there is clearly something to it.Check out also the described indications (like Fibromyalgia) of Milnacipran/Ixel and the few in the same class.And there is this analgetic drug called Nefopam.
 
I think they are trying it out as an antidepressant above all else. Of course, the loss of the -OH means that it no longer follows the 'morphine rule'. I read about it in a German paper on tramadol analogs. Of course, they are using ONE of the two trans isomers whereas tramadol is a mixture of both trans isomers.
 
Faxeladol is a single enantiomer, 3-((1R,2R)-2-((dimethylamino)methyl)cyclohexyl)phenol and has an ED50 of 5.90 mg/kg for opioid-analgesic effects. The opposite enantiomer, 3-((1S,2S)-2-((dimethylamino)methyl)cyclohexyl)phenol, has an ED50 of 1.13 mg/kg. If Faxeladol is prepared from tramadol, which is a racemate, you get the racemate of Faxeladol. To further improve the molecule, the phenolic OH could be acetylated (as in heroin). The final product, Racefaxeladol should be at least equipotent with morphine and can be made in two steps from cheap, commercial tramadol.
 
Yep, you heat in HBr which removes the methyl ether but also dehydrates the alcohol. Then you reduce the double-bond that's formed.

What I would like to see is that Tramadol analog with a F in place of the OH. It's a lot more potent and, of course, you could safely remove the methyl ether.... (then form an ester so you can smoke it :) )
 
Tapentadol is MOR (Acute Pain ) and NERI (Chronic Pain) dual acting drug compared to Tramadol that works only on Mu-Opioid receptor. Can we combine tapentadol with other inhibiotrs such as SSRI or SNRI or DRI to develop an innovative combination?
 
rsesha said:
Tapentadol is MOR (Acute Pain ) and NERI (Chronic Pain) dual acting drug compared to Tramadol that works only on Mu-Opioid receptor. Can we combine tapentadol with other inhibiotrs such as SSRI or SNRI or DRI to develop an innovative combination?
Click to expand...


You're confused. Both are MORA/NARIs, and Tramadol's MORAg effect is minimal.
 
@haribo: why do you think that fluoro-faxeladol is more potent than other tramadol-derivatives? refs?
and why wouldn't the HBr-treated tramadol add the excess HBr to the double-bond; or could you, after removing the HBr, change the reaction conditions and add HF to the double bond?

just some incitations to consider
 
Various monoamine reuptake inhibitors are used as 'analgesic adjuvants', although the GABAminergics are probably the most effective. The efficacy is not just a marketing ploy, but most likely unintentional from the standpoint of drug design.
 
morphiquet said:
@haribo: why do you think that fluoro-faxeladol is more potent than other tramadol-derivatives? refs?
and why wouldn't the HBr-treated tramadol add the excess HBr to the double-bond; or could you, after removing the HBr, change the reaction conditions and add HF to the double bond?

just some incitations to consider
Click to expand...

Probably just maximum electron density or hydrogen bonding ability in that chunk of the molecule?
 
So, what, you joined yesterday and decided to completely ignore the BLUA and all of the forum rules as fast as you could?
 
Sorry, I thought my post was OK with BLUA, but I didn't notice the board rules:) Where can I ask this kind of questions?
 
Nowhere here. Blacklight.in allows synthesis discussion, but there is some restriction put on new members to prevent an influx of "how do I make meth" posts and generally moronic members. The way things are now you'd be able to get a decent answer, however.
 
Flaxeladol, the less opioidergic enantiomer, was patented as fast-acting antidepressant and anxiolytic, superior to venlafaxine and diazepam, respectively. These effects were naloxone-reversible, i.e. caused by µ-opioid stimulation. They didn't do much research with the opposite enantiomer, which is 5 times more potent as opioid. They've probably foreseen trouble with such a potent opioid and the marketing of it. The racemate, which is obtained when plain tramadol is converted to flaxeladol, should have just the right pharmacology: as µ-opioid similar or slightly less potent than morphine, with some added rather weak monoamine reuptake effects, which become effective in the case of abuse of high doses. Estimated dose range: 20 - 200mg, similar to other black market opioids (morphine, heroin, oxycodone), so not too prone for ODs like the ultra-potent opioids some were dreaming of bringing to the market. Raceflaxeladol (suggestions for a better name?), a fast acting antidepressant anxiolytic opioid that's legal and not even an analog should be able to help many people with drug (opioid) problems. Next project: a similar improved, harm reduced replacement for cocaine.
 
I'm not so sure that these wouldn't be considered analogues. They bear striking similarities to the Ampromides and, to a lesser extent, moramides.
 
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