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View Full Version : STRONG opioid with EXCELLENT oral bioavaliability


resorcinol
05-29-2008, 02:44 PM
Well - there is oxycodone, which is moderately strong. However, it's weaker than even morphine when the two are compared administered intraveinously, and morphine isn't all that strong when compared to the range of opioids we have now. Many many opioids are far stronger than morphine is..

Thinking about opioids... I've noticed, in general, they're not the greatest drugs to take orally for anyone with a serious tolerance, with the exception of oxycodone. But even with OC, the doses can get MASSIVE when somebody starts to experiment with stronger opiates via IV, just to get a light buzz, because on the whole oxycodone isn't a very strong opioid.

Of the opioids that are reasonably avaliable, we can say the following:

1. Excellent oral bioavaliability: codeine, dihydrocodeine, hydrocodone, oxycodone, methadone

2. Moderate to poor oral bioavaliability: morphine, hydromorphone, oxymorphone, levorphanol, heroin, fentanyl and it's analogs

What one can quickly notice is that all of the heavyweight opiates that will get someone with a sizeable tolerance off are in the group with poor oral bioavaliability, with the modest exception of oxycodone. This is part of the reason that so many opiate lovers compared to other drug users are self coerced into gravitating towards the needle. Sure, the opiates in group two can give a STRONG buzz orally but you have to take so much more than IV, IM, SC, or plug, that you're left with the feeling that you tragically wasted drugs, and anecdotal evidence suggests that the buzz from even a great opioid is lackluster if taken orally if it's oral bio-a is low, even if you take enough according to charts, when compared to an opioid like oxycodone which is rapidly and completely absorbed orally, and gives a great euphoric buzz orally almost as good as if it was insuffulated or banged. This might be because drugs with poor oral bioavaliability aren't just poorly absorbed, but also erratically absorbed to a varying extent, not allowing that highly euphoric spike in brain levels to occur in one big whoosh.

You'll notice methadone is on the good oral bioavaliability list and is pretty strong. However, methadone is just not really well suited for daily abuse, because it accumulates and clogs the u receptors, essentially blocking it's own euphoric spike. For a chipper it's a darn good choice, but not for most of us here.

So I looked at oxycodone and thought. Oxycodone is the one common opioid that is strong enough to get off a tolerant person and can be taken orally without waste and with a nice buzz by a tolerant person. But it's not without lacking. Taken by IV, it has a weaker rush than other IVable opies, and a VERY tolerant person will need massive, expensive doses to get off, because it's just not THAT strong, and street prices are so marked up.

Clearly, a methyether at position 3 GREATLY improves oral bioavaliability, but sadly, it also weakens the drugs potency. The solution I see?.... keep the 3-methylether and modify the molecule at another spot that can enhance potency to compensate.

Since oxycodone is the most potent of the codone bunch, we start with that. Clearly, a hydroxy substitution at carbon 14 position quite nicely enhances potency... a hydroxy group there is the only difference oxycodone has when compared to hydrocodone.

If we look at oxymorphone research, we find out that esterification of that 14 -OH group greatly increases u receptor affinity and potency. This would work for oxycodone too. cinnamic acid is a great choice as it seems to boost the potency the most of the acids that were studied on oxymorphone.

So the oxycodone ester, 14-cinnamyloxycodone, is the drug I'm looking at (or rather, dreaming of). I predict that 14-cinnamyloxycodone will have a nice solid rush when IVed, have a speedy edge like it's parent drug oxycodone, have a decent duration of action, and have a GREAT ORAL BIOAVALIABILITY allowing doses the same as ones for IV administration to get one off minus the rush. No waste with oral use!

This, my opiophile friends would be a versatile opioid, and this is the one I want to see made, tested, and marketed next (yeah, in my dreams, considering the abuse [aka fun] potential would be TREMENDOUS because of exactly the properties I just described). It would be an amazing, just amazing painkiller for oral use though - I'm sure the CP patient community would root for it.

What do you guys think of 14-cinnamyloxycodone. It'd likely be made as the hydrochloride salt. Hmm, I'd give the pharmaceutical preparation this name:

CincoContin
cinoxycodone HCl

:D:cool:

Tea Time
05-29-2008, 09:33 PM
That's interesting stuff resorcinol!

Question: Have either of these compounds (this one and the one you mentioned in a previous thread) been synthesized and researched at all, or are these hypothetical compounds that you are thinking about? I am just curious...

Indy
05-30-2008, 02:40 AM
Just a note: potency-weight ratio doesn't necessarily make something a "strong" drug. There are quite a few opioids that have very small doses in milligrams equivalent to a dose of another opioid that takes more drug in milligrams, but aren't generally considered as "strong". Fentanyl is dosed in micrograms but it's generally not considered as "strong" as heroin in euphoria or pain relief.

not implying that you didn't know this, just posting this so other people don't get confused.

one thing that ALWAYS bugs me is reading news reports about fentanyl and how it's "a THOUSAND TIMES MORE POTENT THAN HEROIN".

Tea Time
05-30-2008, 09:17 AM
one thing that ALWAYS bugs me is reading news reports about fentanyl and how it's "a THOUSAND TIMES MORE POTENT THAN HEROIN".

Ditto! I know exactly why they do it though: Because it is shocking. Typically they want to take a story that is relatively benign and embellish it until it is shocking and exciting news.

When they mention Fentanyl and it's analogues in the news, they always say that it is 1,000 times stronger than heroin and that it is an extremely dangerous drug that kills huge numbers of people because it is so strong and dangerous.

Unfortunately, the majority of people that watch the news believe what they hear. They buy into all of the exaggeration and the hype and they believe that fentanyl is a dangerous drug that should be taken off the market and kept off the street. :mad:

Sorry for the rant, but I HATE the media...

Papa Verine
05-30-2008, 10:20 AM
I don't know how to synthesize it, but I'm absolutely certain I could abuse it.

I want some!

starglazer33
05-30-2008, 12:39 PM
Awesome thread resorcinal, and I agree with the name you picked out too!

resorcinol
06-01-2008, 04:43 AM
That's interesting stuff resorcinol!

Question: Have either of these compounds (this one and the one you mentioned in a previous thread) been synthesized and researched at all, or are these hypothetical compounds that you are thinking about? I am just curious...

Hydromorphinol has been and is in use (rarely) in some places.

The compound this thread is about... quite possibly has been synthesized, but has never been mentioned in any studies or used. Millions of compounds have been synthesized that aren't mentioned in any publications. That doesn't mean they're no good, just never got tested or got tested on a small scale (possibly, actually likely, if it was tested, not even for human painkilling and euphoric qualities) and weren't put into use.

xDCx
06-10-2008, 06:55 PM
Resorcinol, do you have an account at the Dextroverse with the same name?

resorcinol
06-21-2008, 12:48 AM
Resorcinol, do you have an account at the Dextroverse with the same name?

yep

resorcinol
11-02-2008, 02:14 PM
Just a note: potency-weight ratio doesn't necessarily make something a "strong" drug. There are quite a few opioids that have very small doses in milligrams equivalent to a dose of another opioid that takes more drug in milligrams, but aren't generally considered as "strong". Fentanyl is dosed in micrograms but it's generally not considered as "strong" as heroin in euphoria or pain relief.

not implying that you didn't know this, just posting this so other people don't get confused.

one thing that ALWAYS bugs me is reading news reports about fentanyl and how it's "a THOUSAND TIMES MORE POTENT THAN HEROIN".

Sorry for reviving this thread after so long, but I only just now actually noticed Indy's post. Before I had skimmed over it.

Indy, I agree with you that potency isn't the end all, be all of opioids. Some really potent opioids are less euphoric at equianalgesic doses than weaker opioids and / or have more severe side effects.

However, 14 substituted dihydrocodeinones seem to be a very favored series for abuse due to intense euphoria. My interest here was to make an oxycodone analog that retains the euphoria but is more potent, since oxycodone, while pretty strong, falls just short for peeps with really big gorillas.

I do understand what you're saying, though.

The other benifit would be opening the door for patch formulation of this potent drug, hence lots of drug in a small square package. With the much favored feelings of euphoria from dihydrocodeineones that opiophiles report, the abuse potential would be tremendous I'd suspect... far more than fent.

Sadly, it's exactly that that would likely keep this drug out of clinical trials.

halfalien_s4
11-02-2008, 02:47 PM
Well - there is oxycodone, which is moderately strong. However, it's weaker than even morphine when the two are compared administered intraveinously, and morphine isn't all that strong when compared to the range of opioids we have now. Many many opioids are far stronger than morphine is..

Thinking about opioids... I've noticed, in general, they're not the greatest drugs to take orally for anyone with a serious tolerance, with the exception of oxycodone. But even with OC, the doses can get MASSIVE when somebody starts to experiment with stronger opiates via IV, just to get a light buzz, because on the whole oxycodone isn't a very strong opioid.

Of the opioids that are reasonably avaliable, we can say the following:

1. Excellent oral bioavaliability: codeine, dihydrocodeine, hydrocodone, oxycodone, methadone

2. Moderate to poor oral bioavaliability: morphine, hydromorphone, oxymorphone, levorphanol, heroin, fentanyl and it's analogs

What one can quickly notice is that all of the heavyweight opiates that will get someone with a sizeable tolerance off are in the group with poor oral bioavaliability, with the modest exception of oxycodone. This is part of the reason that so many opiate lovers compared to other drug users are self coerced into gravitating towards the needle. Sure, the opiates in group two can give a STRONG buzz orally but you have to take so much more than IV, IM, SC, or plug, that you're left with the feeling that you tragically wasted drugs, and anecdotal evidence suggests that the buzz from even a great opioid is lackluster if taken orally if it's oral bio-a is low, even if you take enough according to charts, when compared to an opioid like oxycodone which is rapidly and completely absorbed orally, and gives a great euphoric buzz orally almost as good as if it was insuffulated or banged. This might be because drugs with poor oral bioavaliability aren't just poorly absorbed, but also erratically absorbed to a varying extent, not allowing that highly euphoric spike in brain levels to occur in one big whoosh.

You'll notice methadone is on the good oral bioavaliability list and is pretty strong. However, methadone is just not really well suited for daily abuse, because it accumulates and clogs the u receptors, essentially blocking it's own euphoric spike. For a chipper it's a darn good choice, but not for most of us here.

So I looked at oxycodone and thought. Oxycodone is the one common opioid that is strong enough to get off a tolerant person and can be taken orally without waste and with a nice buzz by a tolerant person. But it's not without lacking. Taken by IV, it has a weaker rush than other IVable opies, and a VERY tolerant person will need massive, expensive doses to get off, because it's just not THAT strong, and street prices are so marked up.

Clearly, a methyether at position 3 GREATLY improves oral bioavaliability, but sadly, it also weakens the drugs potency. The solution I see?.... keep the 3-methylether and modify the molecule at another spot that can enhance potency to compensate.

Since oxycodone is the most potent of the codone bunch, we start with that. Clearly, a hydroxy substitution at carbon 14 position quite nicely enhances potency... a hydroxy group there is the only difference oxycodone has when compared to hydrocodone.

If we look at oxymorphone research, we find out that esterification of that 14 -OH group greatly increases u receptor affinity and potency. This would work for oxycodone too. cinnamic acid is a great choice as it seems to boost the potency the most of the acids that were studied on oxymorphone.

So the oxycodone ester, 14-cinnamyloxycodone, is the drug I'm looking at (or rather, dreaming of). I predict that 14-cinnamyloxycodone will have a nice solid rush when IVed, have a speedy edge like it's parent drug oxycodone, have a decent duration of action, and have a GREAT ORAL BIOAVALIABILITY allowing doses the same as ones for IV administration to get one off minus the rush. No waste with oral use!

This, my opiophile friends would be a versatile opioid, and this is the one I want to see made, tested, and marketed next (yeah, in my dreams, considering the abuse [aka fun] potential would be TREMENDOUS because of exactly the properties I just described). It would be an amazing, just amazing painkiller for oral use though - I'm sure the CP patient community would root for it.

What do you guys think of 14-cinnamyloxycodone. It'd likely be made as the hydrochloride salt. Hmm, I'd give the pharmaceutical preparation this name:

CincoContin
cinoxycodone HCl

:D:cool:




actiq &fentora both have really great transmuscoal bioavailability....;)

Narkotikon
11-02-2008, 03:50 PM
Every opiate has great bioavailability if IV'd. :D