Buprenorphine Analogues

[Ham-milton]

It never occured to me that Buprenorphine is schedule 3 (up from C5, why, I dunno), but since it is, it got me thinking- are there any buprenorphine analogues that are in C1 or 2?

MobiusDick mentioned a powerful full agonist analogue "with very interesting euphoriant properties." I'm not sure how to call it, but it'd be Buprenorphine without the N-cyclopropyl but retaining the N-Methyl. He said it was a non-selective mu/delta/kappa agonist. Although I kinda assume that any phenanthrene's are going to be considered analogues, being that this analogue would be so closely related to the parent drug, perhaps it'd avoid it.

 

[dorothyperkins]

I remember F&B saying about how, quite often, replacement of an n-methyl with an n-cyclopropylmethyl switches the effect from agonist to antagonist. Its surely an analog, its got everything morphines got, plus some extra stuff! Is that extra stuff really neccessary? Does N-cyclopropylmethyl morphine have the same partial antagonist effect?

 

[Ham-milton]

Well, buprenorphine is a partial agonist at Mu, and if MobiusDick is correct, this is an agonist.

 

[dorothyperkins]

Yeah thats what i meant, because its lost the cyclopropyl. So do you think replacing the N-Me on morphine with N-cyclopropylmethyl would give a similar partial antagonist, and be much less structurally complex?

 

[immaturepoop]

It never occured to me that Buprenorphine is schedule 3 (up from C5, why, I dunno), but since it is, it got me thinking- are there any buprenorphine analogues that are in C1 or 2?

hey ham-milton! just a quick tidbit. i was told buprenorphine was moved up from schedule V to III after the new high dose formulations of subutex/suboxone came out. i think wikipedia says somptin like that too, but i never really trust wiki 100% on sources. opiate drugs like Butorphanol and Nalbuphine are still schedule IV or V though...

 

[haribo1]

Etorphine

 

[MobiusDick]

Yeah thats what i meant, because its lost the cyclopropyl. So do you think replacing the N-Me on morphine with N-cyclopropylmethyl would give a similar partial antagonist, and be much less structurally complex?

No, it would be a full agonist. The antagonists and partial agonists putatively need an allyl, a methylcyclopropyl or a methylcyclobutyl group; When you start back to an n-pentyl group or an n-phenethyl group, you start getting an even stronger agonist that is typically very euphoric (see phenazocine, although this is a benzomorphan and not a phenanthrene type opioid.) Phenethylnormorphine and particularly phenethylnoroxymorphone are two of the best phenanthrene type opioids I have ever done, and only propionanilides like para-fluorofentanyl can compare to the euphoriant effects. IMO, these types of opioids can over-step high dose methadone, whereas even heroin doesn't give much more than a rush to someone on high dose MMT.

Mobi

 

[MobiusDick]

hey ham-milton! just a quick tidbit. i was told buprenorphine was moved up from schedule V to III after the new high dose formulations of subutex/suboxone came out. i think wikipedia says somptin like that too, but i never really trust wiki 100% on sources. opiate drugs like Butorphanol and Nalbuphine are still schedule IV or V though...

I think C V is about where buprenorphine should be as most people who are opiate users cannot abuse buprenorphine without kicking first. I remember when Nalbuphine was not even scheduled, but butorphanol and nalbuphine seem to be either full antagonists at mu, or at best very, very weak partial agonists. Both have kappa activity and buprenorphine is anecdotally very ineffective when the drug of abuse is butorphanol or nalbuphine.

In the past, the package insert on Buprenex amps had a claim that 0.3 mgs had an equianalgesic dose as morphine, but this is at best true in opioid naive patients. I know in animal surgeries, using buprenorphine or butorphanol is just very ineffective (outside of cats), and some recent studies have come out showing this. It is very obvious anecdotally when the animal comes out of surgery and is given one of these drugs as an analgesic that it is ineffective.

Etorphine and DHE both are similar to the n-methyl dealkylated buprenorphine insofar as they have that large bulky group at the C-6 side of the phenanthrene, which convey orders of magnitude increase in potency as well as delta and kappa effects.

Mobi

 

[immaturepoop]

In the past, the package insert on Buprenex amps had a claim that 0.3 mgs had an equianalgesic dose as morphine, but this is at best true in opioid naive patients. I know in animal surgeries, using buprenorphine or butorphanol is just very ineffective (outside of cats), and some recent studies have come out showing this. It is very obvious anecdotally when the animal comes out of surgery and is given one of these drugs as an analgesic that it is ineffective.


Mobi

hey mob! hmm. quite interesting that you mention the package insert. i remember reading, if im correct, that the 2008 nurses drug handbook claims that 0.3 mg of bupe equals 10 mg of morphine in analgesic potency. i cant remember if it said butorphanol is used for moderate to severe pain though. in comparison only morphine and methadone is said to be used for severe pain only. whereas oxy and hydromorphone says are used for moderate to severe so im not sure. this is what RN's use as a reference at my work.

by the way, ham-milton!

not to be off topic, but out of curiosity, what molecule is your avatar? is it related to methaqualone?

 

[MobiusDick]

hey mob! hmm. quite interesting that you mention the package insert. i remember reading, if im correct, that the 2008 nurses drug handbook claims that 0.3 mg of bupe equals 10 mg of morphine in analgesic potency. i cant remember if it said butorphanol is used for moderate to severe pain though. in comparison only morphine and methadone is said to be used for severe pain only. whereas oxy and hydromorphone says are used for moderate to severe so im not sure. this is what RN's use as a reference at my work.

by the way, ham-milton!

not to be off topic, but out of curiosity, what molecule is your avatar? is it related to methaqualone?

There have been some studies about the Nasal version of Stadol (butorphanol) working much better in women than in men since most if not all of its activity is from kappa agonism. It was hypothesized that this is related to child birth.

This subsequent addition is my little hypothesis here so I cannot give you a reference, but my logic is this: since kappa does not cause the respiratory depression that is seen with mu agonists, there is a logical reason why Dynorphin A may be released during child birth and have a far greater analgesic effect in women, particularly with spinal analgesia (in which kappa/Dynorphin A has a larger role than endorphins and endomorphins perinatally.)

Mobi