At the end of the tunnel

[stvip]

Skimming over some fascinating* facts about this molecule, here's a a little excerpt:

"In view of the high opioid agonist potency of MDAN-21 and its absence of tolerance and physical dependence, we determined its i.v./i.c.v. potency ratio and compared it to that of morphine to estimate its relative ability to penetrate the brain. The data revealed that MDAN-21 was 50-fold more potent than morphine, whereas the i.v./i.c.v. potency ratio was identical (http://www.pnas.org/math/ap.gif40, Table 4 (http://www.pnas.org/cgi/content/full/102/52/19208#TBL4)). These results suggest that the parenteral bioavailability of these compounds are similar. Given its much higher potency and its inability to produce tolerance and physical dependence in mice, MDAN-21 offers an approach for the development of potent, bioavailable analgesics devoid of these side effects."

PNAS | December 27, 2005 | vol. 102 | no. 52 | 19208-19213

Now off to the lab with you. When come back bring MDAN-21.

*being a geek aids in the consummate achievement of fascination (the achievement of fornication is left as an exercise to the reader).

[jacky]

MDAN 21 is great stuff, I love it.

[doctor diesel]

MDAN 21 is great stuff, I love it.


So.... where to find it, Jacky?


Your Doc.

[stvip]

MDAN 21 is great stuff, I love it.

You love the idea and experimental findings, or have you actually assayed it (in which case, the people demand to hear every detail you can divulge, and some that you can't)? This simple rationally designed drug (delta antagonist-morphine agonist dimer) could be revolutionary.

[Mokelly]

yeah jacky, what's up? You actually have tried MDAN-21????

[defenestrate]

wow-gotta find out more about this stuff.

[jacky]

no...I was full of shit...probably wrote that under the influence of glue or something.

sorry...
I dont do that too often

sounds amazing though...

what the opiate undergroung needs is motivated chemists and a motivation towards R and D....instead of making an opiate as potent as possible, make an opiate that allows the user to lead a more normal life...thus insureing that they will be there tomorrow to buy more product.

[exitwound]

It's certainly come up on every opiate-related site and forum I've ever been on, the serious-minded ones anyway. But I've never heard of anyone getting their hands on so much as a single dose.....unfortunately development of these promising compounds is not proceeding nearly fast enough. Many of them do not seem to appeal to the major pharm-chem corporations for some reason. I guess it's not profitable enough to develop superior solutions for pain :mad:

[superman]

isn't heroin enough? i am content with hydromorph, or oxy, morphine, even fentanyl does me good for a couple weeks.

the thing about these synthetics is that the developers are typically not targeting the mu receptors. and as we all know that's where the bliss is. they expect some magic bullet to be discovered in which euphoria and pain relief walk separate lines. well fuck them, instead support the poppy farmers of the world.

[exitwound]

they would be enough if they were so easily and freely/cheaply available that you could just keep taking more for an almost unlimited dose curve. but until that day comes, we will always hope for better solutions to the age-old problems that opiates bring with them.

[stvip]

There is no reason to assume MDAN-21 would not be highly euphoric. Its mu-agonist pharmacophore is oxymorphone. This research is further proof (there are others) that the euphoric and analgesic effects of opioids are not inextricably tied to dependence and tolerance. Besides serving as further proof, MDAN-21 (and possibly other molecules following its structural design) also seems like a promising practical embodiment of a non physically addictive opioid.

[newParadigm]

this sounds truly promising.

[Dexter the Meth Orphan]

this sounds truly promising.

It sure does...MDAN 21, I want thee!

[Hammilton]

where can i find the molecular structure? I can't find much besides the initials

[jonny-5]

this is freaking awesome. hopefully theyll pass it out to all of us trying to maintain. it would be pretty cool to be getting loaded and still be able to take a plane ride without having to smuggle an assload (not literally hahah) of whatever to your destination.

[Hammilton]

sure woudl save a lot of trouble.

[stvip]

where can i find the molecular structure? I can't find much besides the initials

It's in the paper, of course.
The molecule is a rationally designed drug - that is, it was artificially constructed precisely according to some plan, instead of a compound found in nature or one modified from such more or less randomly.

What they did is take a the active moiety (pharmacophore) of oxymorphone (mu agonist) and natrindole (delta antagonist) and joined them together with a bridge of carbon atoms. This created the MDAN-X series, with "X" being the number of atoms separating the two moieties. They designed it thusly because of findings of reduced tolerance/dependence with combinations of mu-agonists and delta-antagonists, along with the recent findings about the nature of opioid receptor binding and opioid receptor subtypes (which are now believed to actually be different dimerizations of the various receptors, but the issue is complex). MDAN-21 was found to have optimal properties.

[Hammilton]

thanks, that's enough of a starting place for me right now. There have been a lot of natrindole-derived drugs being studied, actually.

I wonder why the chose oxymorphone as the mu-agonist to work with though. Potency, probably? It certainly wasn't euphoria, unfortunately

[Dilaudid]

Hello Hammilton,

thanks, that's enough of a starting place for me right now. There have been a lot of natrindole-derived drugs being studied, actually.

I wonder why the chose oxymorphone as the mu-agonist to work with though. Potency, probably? It certainly wasn't euphoria, unfortunately

The disign of this drug was ingenious much more than a MOR agonist and a DOR agonist administred together.
You can easyly change the µ pharmacophore by hydromorphone and so on...

best regards Dilaudid.

[Hammilton]

Dilaudid, I'm visiting parents for the next few days and won't be able to AIM ya, but I was wondering if you were able to put together an image of MDAN-21?

[stvip]

Update. This will be viewed as bad news by some, excellent by others:
Absence of conditioned place preference or reinstatement with bivalent ligands containing mu-opioid receptor agonist and delta-opioid receptor antagonist pharmacophores.


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17383633&query_hl=6&itool=pubmed_docsum

[euphoria2002]

Update. This will be viewed as bad news by some, excellent by others:
Absence of conditioned place preference or reinstatement with bivalent ligands containing mu-opioid receptor agonist and delta-opioid receptor antagonist pharmacophores.


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17383633&query_hl=6&itool=pubmed_docsum

Now if you can explain what that means in english.....:)

[stvip]

Now if you can explain what that means in english

The test for "conditioned place preference" is an animal model used for predicting the rewarding effects of a drug (which translates to euphoria in man). As the name implies, the researchers see whether animals administered a compound develop a preference for the place in which they receive it. This study shows that the MDAN molecules previously shown to have full antinociceptive potency, but lacking a tolerance or dependence effect, also seem to lack a reward effect.

[bronyraur]

This study shows that the MDAN molecules...also seem to lack a reward effect.

HALT all research.

No reward effect=brony not interested.

[Hammilton]

hah definitely, lol.

I'd like to see what sort of sedation it produced. There are more than a couple opioids that in humans have been widely abused, but in animals addiction was not seen. I'm thinking Pentazocine, in at least one primate study of abuse potential was found to not be abuse-prone.

Caffeine was shown to have that potential, though. LOL

[stvip]

No reward effect=brony not interested.

Right, but no tolerance or dependence means doctors would prescribe this class of opioids to the exclusion of all others, and for them, lack of euphoria (which they consider a toxic side effect) is a huge bonus. Even if everything goes smoothly for this compound (and class of compounds) marketing is still about a decade away, but if it reaches that stage while showing the same type of effects seen in preclinical tests, it will drastically change pain management and the availability of legal euphoric opioids.