neuromodulator (Stranger)
01-07-02 00:23
No 253336
      2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   

Early on in his career, Shulgin writes of trying to find a PEA that would resemble THC.  He had no luck.  However, he apparently overlooked the most obvious substrate, olivetol.

Olivetol, which is available commercially for about $100 for 10 g, is 1,3-dihydroxy-5-n-pentylbenzene and could be methoxylated, formylated, condensed with EtNO2 and reduced to form 2,6-dimethoxy-4-n-pentylamphetamine.

Yes, I know that THC _supposedly_ works by stimulating the anandamide receptor, but I would still be willing to bet
$100 that this compound would fuck you up with 10 mg.

Still, I don't have the ways or means of producing it.  Is there anybody out there who wants to bring this compound to fruition and has the capability of doing so, or is this another stupid idea?

Just curious...
 
 
 
 
    Rhodium
(Chief Bee)
01-07-02 00:40
No 253340
      Re: 2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   

See the file ../rhodium/chemistry /246labrat.html for ideas for your synthesis.
 
 
 
 
    Osmium
(Stoni's sexual toy)
01-07-02 03:54
No 253394
      Re: 2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   

I seem to remember that longer than 3 or 4 C alkyl chains aren't that desirable and VERY slow and long acting.
 
 
 
 
    Rhodium
(Chief Bee)
01-07-02 04:30
No 253412
      Re: 2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   

Osmium: You are probably right, but that theory hasn't been proven with 2,4,6-substituted phenetylamines, right? wink
 
 
 
 
    neuromodulator
(Stranger)
01-07-02 22:31
No 253695
      Re: 2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   

Comparing 2,6-dimethoxy-4-n-pentylamphetamine to DOAM is like comparing TMA-6 to TMA-2.  They might be completely different.  And if psi-DOAM lasts a long time, then that's even better (especially if it's as good as marijuana).
 
 
 
 
    Lilienthal
(Moderator)
01-08-02 11:15
No 253959
      Re: 2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   

Sounds interesting, but I would bet that the C5 chain makes it an antagonist at the 5-HT2A receptor and thereby inactive as a psychedelic.
 
 
 
 
    Antoncho
(Official Hive Translator)
01-08-02 14:24
No 253999
      Re: 2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   


I would bet that the C5 chain makes it an antagonist at the 5-HT2A receptor and thereby inactive as a psychedelic.




thus making it a useful antipsychotic....

Antoncho

 
 
 
 
    Rhodium
(Chief Bee)
01-08-02 14:33
No 254002
      Re: 2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   

It need not be useful - even if it is an antagonist, it might have exceptionally low binding affinity/specificity.
 
 
 
 
    neuromodulator
(Stranger)
01-08-02 22:31
No 254122
      Re: 2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   

Before I posted here, I emailed Dr. Dave Nichols at Purdue U. about this compound.  This is how he replied:

"The only 2,6-dimethoxy compounds I know of are the 4-methyl, 4-methylthio, and 4-bromo [apparently he forgot about TMA-6], the latter two of which have not been studied in man (or rats).

"Shulgin has published work showing that the human activity drops off after the length of the alkyl chain in the 4-position exceeds n-propyl.  Based on similar docking in the receptor for the 2,6- versus the 2,5- orientations (something we believe is close to the truth but is not proven), one would thus predict, a priori, that a 2,6-dimethoxy-4-pentylamphetamine would not be a hallucinogen, although it might have high affinity for the serotonin 2A receptor, based on studies done by Glennon on 5-HT2A antagonists.

"All of the classical hallucinogens appear to activate the serotonin 2A receptor, whereas THC apparently activates an anandamide receptor in the brain, designated the CB1 (cannabinoid 1) receptor, which has a completely different function and activation requirement than the 5-HT2A receptor.  Thus, no studies have been able to show any similarity of THC to things like LSD, and there have been several that were done years ago.  It is my understanding that high doses of THC can produce a profound hallucinogenic state, but I have my doubts that it is very similar to the effect of LSD."

***

Again, I am not looking for a classical hallucinogenic compound.  I am looking for a compound that gets you very, very stoned (i.e., the "profound hallucinogenic state" he refers to).  I guess there's only one way to find out more about this compound, but again, I am not able to do it myself. 

As for the 5-HT2A antagonism angle, DOAM appears to be active (whether or not it antagonizes the 5-HT2A receptor or not I don't know).
 
 
 
 
    yellium
(Hive Addict)
01-08-02 23:01
No 254129
      Re: 2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   

IIRC, there was a also study of Glennon which showed that the binding affinity of 2,5-dimethoxy-n-alkyl-amphetamines  increased to n=3 (or 4), and then stayed at approximately the same level, or even getting slightly larger, which does not match with the human activity data. Even worse: a substituted compound (something like t- or s-butyl) had a comparable affinity as n-butyl.  Which only serves to say that numbers aren't everything.
 
 
 
 
    neuromodulator
(Stranger)
01-10-02 21:20
No 254883
      Re: 2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   

The "human activity data," I presume, comes from Shulgin.  Shulgin's test population was what, n=3 or 4?

And lsd is a mixed 5-HT2a receptor agonist/antagonist, but I don't see anyone clammoring to use it as an atypical antipsychotic.

2,6-dimethoxy-4-n-pentylamphetamine has the potential to be the next big drug for many reasons.  Its synthesis requires no alkylation or de novo methoxylation of a fickle benzene ring (unless you count formylation as an alkylation; still formylation of olivetol is not nearly as complex as synthesizing, say, 1,3,5-triethylbenzene).  Olivetol is an uncontrolled natural product much like sassafras oil once was whose "aromatic fingerprint" (i.e., electron charge distribution) is similar if not identical to THC's at their respective aromatic rings.  And, compared to indanyl(meth)amphetamine, the reagents required for its synthesis are mundane, albeit watched.  Even Nichols admits that the assumption that the 2,4,5-substitution pattern has the same activity as that of the 2,4,6-pattern is completely unproven.  If this compound doesn't deserve more attention, then I don't know what does (other than indanyl(meth)amphetamine).  Rhodium?
 
 
 
 
    Rhodium
(Chief Bee)
01-10-02 22:41
No 254903
      Re: 2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   

Yes, the postulate that all 2,4,6- compounds are as active as the 2,4,5- compounds is unproven, but in every case the 2,4,6- analog of something has been made, it has worked perfectly, so it is still probable, even if it not proven.
 
 
 
 
    neuromodulator
(Stranger)
01-11-02 02:08
No 254960
      Re: 2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   

So do you think that this is a promising compound?
 
 
 
 
    Rhodium
(Chief Bee)
01-11-02 03:33
No 255012
      Re: 2,6-dimethoxy-4-n-pentylamphetamine  Bookmark   

I think it would be active, yes, but it is impossible to tell if it would be "good" or not. I would guess the activity would be around 50mg and have a very long duration, considering the DOPR/DOBU/DOAM entries in Pihkal...