resorcinol
02-27-2009, 09:36 PM
-like opioids.
*Note: I don't think this has any pharmacodynamic relevance whatsoever, but it's still cool.
Morphine like (phenanthrene) opioids are phenethylamines! Take a look:
Oxycodone:
http://upload.wikimedia.org/wikipedia/commons/d/de/Oxycodone.png
This applies to morphine too but it's easier to see in this particular image of oxycodone's structure.
Start at the aromatic ring and move towards the amine group. There's a two carbon spacer (ethyl) separating the benzene ring from the amine. That's the phenethylamine backbone. See it? Isn't it pretty cool? Edit: Actually, not only does it have the phenethylamine backbone, it has the entire methamphetamine backbone too!
It may have some relevance in that perhaps dual mu agonist and DNRI/DA & NE releasing stimulants could be developed. We do have one: lefetamine. Maybe there are more potent analogs though.
Lefetamine isn't a phenanthrene opioid though. I seriously doubt a full classical phenanthrene opioid could ever be a monoaminergic stimulant: they're too bulky. But simplified stuctures like lefetamine clearly can be.
Talk about addictive... lefetamine is probably insanely addictive: it's a speedball in one drug. On the flip side, since DA & NE releasing and DNRI stimulants have been shown to have analgesic activity (mechanism not really known), I bet lefetamine is a very powerful painkiller, probably superior to morphine, with the plus of the unwanted side effects of both psychomotor stimulation and opioid mu agonism canceling out (somnolence canceled by stimulation, and tweakiness canceled by mu agonism). Fat chance we'll ever see lefetamine or any drug like it marketed as an analgesic though: the addiction potential is probably phenominal. I don't, however, see the concern doctors have in general about terminally ill and/or very old patients becoming addicted: why does it matter at that point? It boggles my mind. I think a lefetamine like drug could be a godsend for these types of patients, since often the massive opioid doses they require make them very quiet, reclusive, and head-in-clouds distracted. Their family might appreciate an opioid that actually helps the dying family member open up to them rather than sedating them into reclusion and space cadet land, thanks to the dual mode action as in lefetamine.
Lefetamine can also likely provide the same analgesia of plain mu agonists with less mu agonism since monoaminergic stimulation is also analgesic; this would mean less physical dependence (at the cost of higher risk of psychological addiction, but in terminal patients, why do people care so much? They're dying. Let them take whatever dope they want as long as no serious contraindications are present).
Edit2: If you look at lefetamine's structure, it's an extremely stripped down phenanthrene derived structure (with some other glaring differences like the amine having two methyl groups [in classic phenanthrenes that makes it a quaternary ammonium salt and nearly completely abolishes activity] and there are two aromatic rings on the sides of the molecule instead of one aromatic, and one cyclopent-7,8-ene like in classic phenanthrene opioids, the THF ring is totally gone in lefetamine, and the non-aromatic ring is opened, and finally, the fourth ring is totally done away with --- but you can still see the structural similarities). Much of the bulk is removed, allowing for DNRI activity to manifest since its structure resembles methylphenidate AND phenanthrene opioids, the latter of which gives mu agonist activity (although it is NOT a phenanthrene since the middle ring is opened and the other things mentioned above). Sure, you'll never reach the potency of some of the bulky true phenanthrene opioids at mu agonism due to the stripped down structure, but the psychomotor stimulant activity makes up for the lessened opioid mu mediated analgesia.
lefetamine
http://upload.wikimedia.org/wikipedia/commons/thumb/4/4b/Lefetamine.svg/130px-Lefetamine.svg.png
^It's probably a bit weaker than morphine as a mu agonist, but a superior analgesic overall b/c of the DNRI activity.
*Note: I don't think this has any pharmacodynamic relevance whatsoever, but it's still cool.
Morphine like (phenanthrene) opioids are phenethylamines! Take a look:
Oxycodone:
http://upload.wikimedia.org/wikipedia/commons/d/de/Oxycodone.png
This applies to morphine too but it's easier to see in this particular image of oxycodone's structure.
Start at the aromatic ring and move towards the amine group. There's a two carbon spacer (ethyl) separating the benzene ring from the amine. That's the phenethylamine backbone. See it? Isn't it pretty cool? Edit: Actually, not only does it have the phenethylamine backbone, it has the entire methamphetamine backbone too!
It may have some relevance in that perhaps dual mu agonist and DNRI/DA & NE releasing stimulants could be developed. We do have one: lefetamine. Maybe there are more potent analogs though.
Lefetamine isn't a phenanthrene opioid though. I seriously doubt a full classical phenanthrene opioid could ever be a monoaminergic stimulant: they're too bulky. But simplified stuctures like lefetamine clearly can be.
Talk about addictive... lefetamine is probably insanely addictive: it's a speedball in one drug. On the flip side, since DA & NE releasing and DNRI stimulants have been shown to have analgesic activity (mechanism not really known), I bet lefetamine is a very powerful painkiller, probably superior to morphine, with the plus of the unwanted side effects of both psychomotor stimulation and opioid mu agonism canceling out (somnolence canceled by stimulation, and tweakiness canceled by mu agonism). Fat chance we'll ever see lefetamine or any drug like it marketed as an analgesic though: the addiction potential is probably phenominal. I don't, however, see the concern doctors have in general about terminally ill and/or very old patients becoming addicted: why does it matter at that point? It boggles my mind. I think a lefetamine like drug could be a godsend for these types of patients, since often the massive opioid doses they require make them very quiet, reclusive, and head-in-clouds distracted. Their family might appreciate an opioid that actually helps the dying family member open up to them rather than sedating them into reclusion and space cadet land, thanks to the dual mode action as in lefetamine.
Lefetamine can also likely provide the same analgesia of plain mu agonists with less mu agonism since monoaminergic stimulation is also analgesic; this would mean less physical dependence (at the cost of higher risk of psychological addiction, but in terminal patients, why do people care so much? They're dying. Let them take whatever dope they want as long as no serious contraindications are present).
Edit2: If you look at lefetamine's structure, it's an extremely stripped down phenanthrene derived structure (with some other glaring differences like the amine having two methyl groups [in classic phenanthrenes that makes it a quaternary ammonium salt and nearly completely abolishes activity] and there are two aromatic rings on the sides of the molecule instead of one aromatic, and one cyclopent-7,8-ene like in classic phenanthrene opioids, the THF ring is totally gone in lefetamine, and the non-aromatic ring is opened, and finally, the fourth ring is totally done away with --- but you can still see the structural similarities). Much of the bulk is removed, allowing for DNRI activity to manifest since its structure resembles methylphenidate AND phenanthrene opioids, the latter of which gives mu agonist activity (although it is NOT a phenanthrene since the middle ring is opened and the other things mentioned above). Sure, you'll never reach the potency of some of the bulky true phenanthrene opioids at mu agonism due to the stripped down structure, but the psychomotor stimulant activity makes up for the lessened opioid mu mediated analgesia.
lefetamine
http://upload.wikimedia.org/wikipedia/commons/thumb/4/4b/Lefetamine.svg/130px-Lefetamine.svg.png
^It's probably a bit weaker than morphine as a mu agonist, but a superior analgesic overall b/c of the DNRI activity.