N,N-Dimethyltyrosine: The Viagra of Opioids

[Hammilton]

I have no idea why they call it thus, you know, the chinese. But they have. I've often thought that DMTyr would be an opioid, and it turns out that it is. There are also many dimethyltyrosine-structure containing opioids out there, some of which are especially potent.

Perhaps if instead of rocket parts the Chinese sold Kim Jong Il some of this he'd be less inclined to launch TPD-2's at HI. I guess we'll see if missle defense was worth it. But seriously, why HI? They should be able to easily reach AK no? Why not do that instead of going for a long shot at HI? Their missles aren't exactly great. I suppose Kim wants to finish out the war before he dies. I wonder how eager to go the average north korean foot soldier will be just to make Dear Leader happy.

doi:10.1016/S1005-9040(06)60092-5

Copyright © 2006 Jilin University Published by Elsevier Ltd
Dimethyltyrosine, the Viagra of Opioids

This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier.
Lawrence H. Lazarusa, , , Sharon D. Bryanta, Severo Salvadorib, Remo Geurrinib, Gianfranco Balbonic, Yuko Tsudad and Yoshio Okadad

aPeptide Neurochemistry, LCBRA, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA

bDepartment of Pharmaceutical Science, University of Ferrara, I–44100 Ferrara, Italy

cDepartment of Toxicology, University of Cagliary, Cagliary 109126, Italy

dFaculty of Pharmaceutical Science, Kobe Gakuin University, Nishi-ku, Kobe 651-2180, Japan


Received 20 December 2005. Available online 18 April 2006.

Keywords: Dimethyltryrosine; Opioid; Agonist

 

[ausser_betrieb]

sounds really intresting! good find. anyone further information?

 

[MurphyClox]

Not N,N-DiMe-Tyr but rather 2',6'-DiMe-Tyr was described with the following properties:

The 2′,6′-dimethyl-l-tyrosine (Dmt) enhances receptor affinity, functional bioactivity and in vivo analgesia of opioid peptides. To further investigate its direct influence on these opioid parameters, we developed a series of compounds (H–Dmt–NH–X). Among them, H–Dmt–NH–CH3 showed the highest affinity (Kiμ = 7.45 nM) equal to that of morphine, partial μ-opioid agonism (Emax = 66.6% ) in vitro and a moderate antinociception in mice.

Ref: Bioorg Med Chem Lett 2005, 15(3), 599
DOI: 10.1016/j.bmcl.2004.11.040

Who said that the 2 methyls are placed at the nitrogen?

- Murphy

 

[permastoned]

Haha I get it.. its the viagra of the opioids because it makes the opioid peptides stronger (through enhanced affinity).. Crazy Chinese. I wonder how.. if it worked on all opioids, then clearly the implication is that it must act on the opioid receptors to increase their affinity somehow, through some sort of conformational change.

But assuming it only works on the peptides, I would assume it perhaps binds to the peptide and increases its receptor affinity.

It is impressive that H-Dmt-NH-CH3 is so strong at doing so that it is equally as potent as morphine. Hold up, then it says it has partial mu agonism in vitro. Confused now.. I thought the indication was that Dmt and its derivatives increased opioid peptide affinity rather than binding themselves. Or maybe they do both?

Very Curious.

Evidently selegiline is the viagra of the DRIs!

 

[Hammilton]

Wait does anyone actually have THIS paper?

I'm confused now too.

 

[permastoned]

Do now.. thanks uni

Not quite what we thought. It is about modifying opioid peptides (the tyrosine)

The common N-terminal amino acid of endogenous opioid
peptides (enkephalins,1 endorphins,2 dynorphins,3
endomorphins,4 deltorphins,5 dermorphins,6 and so
on) is Tyr, except Phe in nociceptin,7 and is considered
an important pharmacophore to interact with opioid
receptors according to the message–address concept.8
Recent studies verified that Dmt (20,60-dimethyl-L-tyrosine)
9 can readily replace Tyr in opioid substances and
dramatically enhances receptor affinity, in vitro functional
bioactivity and in vivo analgesic action.10 For
example, affinity increased by several hundredfold for
enkephalin derivatives, such as [Leu5]enkephalin11 and
DPDPE (cyclo[D-Pen2,5]enkephalin),12 the dermorphin
analogue DALDA (H-Tyr-D-Arg-Phe-Lys-NH2),13 deltorphin,
14 and endomorphin-2 (EM-2)15 as well as the
Tic-containing di- and tripeptide DOR (d-opioid receptor)
antagonists.10,16

 

[Hammilton]

I came across this paper while searching out N,N-dimethyltyrosine, and guess I assumed that it was actually about that.

 

[PsychedelicPeptide]

You guys should be looking into the opioid peptides (and analogs) themselves I think. There are a lot of short peptides with agonist activity at all the receptors (mono-agonists, co-agonists, etc) which to what I am aware of are totally unexplored in terms of their recreational use potential. A lot of progress has been made in the field in the past 5 years or so.

The right analog in form of an intranasal spray might just knock your socks off. =O

 

[permastoned]

I came across this paper while searching out N,N-dimethyltyrosine, and guess I assumed that it was actually about that.

Oh, sorry, my mistake. I do not have the viagra of opioids paper. Only the one that Murphy posted. However, considering the title, I would assume it was a similar sort of dealio.

 

[Coolio]

But seriously, why HI? They should be able to easily reach AK no? Why not do that instead of going for a long shot at HI? Their missles aren't exactly great.

Population density of Hawaii is 188 per square mile. Population density of Alaska is 1 per square mile. Does that answer your question?

 

[Hammilton]

Yeah, but obviously they won't be doing this to kill people. There are far better ways of doing that. Unless of course they load it with one of their nukes, but I doubt they're going to do that given the propensity for the TPD-2 to fail.