Benzomorphan SAR

[haribo1]

Although there are quite a few benzomorphans tested, to my knowledge only 4 have ever reached the market. Those are matazocine, phenazocine, pentazocine and dezocine. The skeleton has some interesting features. I cannot find an instance of a pure antagonist for starters; Pentazocine is a mixed agonist/antagonist.
What makes it interesting to me is that the X & Y substituants above can be tweeked to increase potency and agonist/antagonist ration treeked. All potencies are relative to morphine.

X
--

-Methyl is RP = 0.4
-Phenylethyl = 4
-2Thienylethyl = 16


Y
--

-OH = 1.0
-NO2 = 10


So, this very scruffy research reveals that the optimal N-substituant is 2 thienyl ethyl and the optimal substituant on the benzene ring is a nitro. This compound IS 160x morphine putting it in the class with fentanyl and such. I should add that adding a NO2 to the phenanthracine opioids (like morphine itself) doesn't increase activitity, but it IS still active.

 

[Ham-milton]

The problem with these, imho is that they have agonist activity at too many types of opioid receptors- primarily kappa receptors.

A long lasting salvia trip that's actually euphoric is such a bad idea. Even if you could get a pure mu-agonist, I doubt you can negate kappa agonism on these.

 

[haribo1]

The mu-Kappa ratio of phenazocine, at least, is about 20:1 so it doesn't cause any problems. I know some other N substitutions (with odd cyclic groups) sure did have that problem.

 

[Ham-milton]

Pentazocine was horrible in that respect.

 

[haribo1]

^Yep, they sure ended up with an almost non-abusable drug there. In fact, some people DID abuse it by mixing with tripelenamine ans shooting it. I think they must have been desperate. Eventually naloxone was added to the tablets...

 

[Holy_cow]

If you search hard enough, you'll find N-normetazocine is commercially available .

 

[haribo1]

^Ahem.... I wan't going to mention that, but yes, that's true. Now, question, what's the easiest way to change that -OH into an NO2? That would safely take it off the MOdA (but not US analog laws) But at least it's 10 times stronger.

 

[fastandbulbous]

If you search hard enough, you'll find N-normetazocine is commercially available .

If you have enough money, anything is commercially available: I bet Bill Gates could get himself a nice critical mass of Russian plutonium if he really really wanted it. The problems start with the follow up visits to see what you're doing with it

Oh and this is effectively a sourcing post, so we'll have no more such talk unless you want an angry f&b or vecktor on your case

 

[Ham-milton]

If you have enough money, anything is commercially available: I bet Bill Gates could get himself a nice critical mass of Russian plutonium if he really really wanted it. The problems start with the follow up visits to see what you're doing with it

And he has good uses for it. Like when he decides he's had enough EU Anti-trust bitching. Or when he decides to make war on South Africa.