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N&PD Moderators: Skorpio | someguyontheinternet
Possible Drugs of the Future
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fastandbulbous
Bluelight Crew
Belisarius
They look a hell of a lot like the tetralin derivitives that are direct dopamine agonists (DPAT- N,N-dipropyl-2-aminotetralin derivitives). They'll have the same structural configuration, and most prob the same 1-octanol/water partition coefficient (gives blood brain barrier penetration comparison), so most probably act in the same way
They look a hell of a lot like the tetralin derivitives that are direct dopamine agonists (DPAT- N,N-dipropyl-2-aminotetralin derivitives). They'll have the same structural configuration, and most prob the same 1-octanol/water partition coefficient (gives blood brain barrier penetration comparison), so most probably act in the same way
rachamim18
Bluelighter
Fast and Bel...
But if the BBB penetration was dealt with they would be a very interesting possibility. The wave of the future.
But if the BBB penetration was dealt with they would be a very interesting possibility. The wave of the future.
fastandbulbous
Bluelight Crew
Opiate chemical groups
I said I’d do this a while ago (then again I’m a lazy sod at times), but eventually, a list of the main groups of opiates, with a few examples of each.
The main requirement for opiate activity is shown below (R’s represent alkyl, cycloalkyl, alkenyl etc – you get the drift)
Drugs derived from morphine’s structure
a) gives the modified structure to give dihydromorphine
b) gives the modified structure to give hydromorphone
c) gives the modified structure to give oxymorphone
d) is a modification that produces a drug about 20x the potency of morphine
For the corresponding codeine derivatives, the 3-hydroxy group is replaced by a 3-methoxy group. Heroin is the 3,6-diacetyl ester of morphine.
Removing the oxygen bridge (4,5 position) produces the morphinan series
Using thebaine as the starting material produces high potency oripavine series drugs
Replacing the saturated ring that carries the 6-OH group of morphine with two methyl groups, produces the benzomorphans
These tend to be partial mu agonists, some with partial kappa agonist activity as well (eg pentazocine)
Methadone derivatives, at first sight appear to have little in common with morphine, but do fit the requirements for opiate activity, and can spatially arrange themselves in the same way as morphine
Altering the methadone structure further, can give compounds with varying degrees of agonist activity
I said I’d do this a while ago (then again I’m a lazy sod at times), but eventually, a list of the main groups of opiates, with a few examples of each.
The main requirement for opiate activity is shown below (R’s represent alkyl, cycloalkyl, alkenyl etc – you get the drift)
Drugs derived from morphine’s structure
a) gives the modified structure to give dihydromorphine
b) gives the modified structure to give hydromorphone
c) gives the modified structure to give oxymorphone
d) is a modification that produces a drug about 20x the potency of morphine
For the corresponding codeine derivatives, the 3-hydroxy group is replaced by a 3-methoxy group. Heroin is the 3,6-diacetyl ester of morphine.
Removing the oxygen bridge (4,5 position) produces the morphinan series
Using thebaine as the starting material produces high potency oripavine series drugs
Replacing the saturated ring that carries the 6-OH group of morphine with two methyl groups, produces the benzomorphans
These tend to be partial mu agonists, some with partial kappa agonist activity as well (eg pentazocine)
Methadone derivatives, at first sight appear to have little in common with morphine, but do fit the requirements for opiate activity, and can spatially arrange themselves in the same way as morphine
Altering the methadone structure further, can give compounds with varying degrees of agonist activity
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fastandbulbous
Bluelight Crew
Continued
Cont...
The other big group of opiate-like drugs come from the 4-phenylpiperidine derivatives
Also seen as a variation of the 4-phenylpiperidines, are the fentanyl derivatives. While not strictly adhering to the template structure for opiate activity, they contain some of the most potent agonist around (alpha-methylcarfentanyl is a suggestion for an opiate with a silly potency, it would be so active)
Among the other opiate-like activity structures are the thiambutenes, which have only been used in Japan
And the benzimidazoles. These have not been used clinically, but etonitazene has an activity of aprox 1000x that of morphine. Although a whole series exist, the only ones to find their way into legislation are etonitazene and clonitazene.
Most designer opiates encountered in the illicit market are likely to come from the 4-phenypiperidine and fentanyl groups (ease of synthesis), but there is a lot of potential for the benzimidazole derivatives (etonitazene etc).
If I’ve missed any out, please add them below
Cont...
The other big group of opiate-like drugs come from the 4-phenylpiperidine derivatives
Also seen as a variation of the 4-phenylpiperidines, are the fentanyl derivatives. While not strictly adhering to the template structure for opiate activity, they contain some of the most potent agonist around (alpha-methylcarfentanyl is a suggestion for an opiate with a silly potency, it would be so active)
Among the other opiate-like activity structures are the thiambutenes, which have only been used in Japan
And the benzimidazoles. These have not been used clinically, but etonitazene has an activity of aprox 1000x that of morphine. Although a whole series exist, the only ones to find their way into legislation are etonitazene and clonitazene.
Most designer opiates encountered in the illicit market are likely to come from the 4-phenypiperidine and fentanyl groups (ease of synthesis), but there is a lot of potential for the benzimidazole derivatives (etonitazene etc).
If I’ve missed any out, please add them below
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PEPAP has a phenylethylchain. By using a cinnamoyl or phenylpropyl chain compounds of greatly enhanced potency can be obtained. This is unlikely however, as THP derivatives may or may not be formed as a by-product. In any event such a drug is already covered in the uk under the pethidine laws.
Lefetamine is another good opiate that has been banished and is under recognized.
Any idea why levophanol is not more widely known. It seems like drug companies are almsot exclusively producing stereoselective DXM.
Lofentanil 3-Me-Carfentanil is the most potent opioid that has been made almost. As well as being ridiculously toxic it is also very long acting.
Lefetamine is another good opiate that has been banished and is under recognized.
Any idea why levophanol is not more widely known. It seems like drug companies are almsot exclusively producing stereoselective DXM.
Lofentanil 3-Me-Carfentanil is the most potent opioid that has been made almost. As well as being ridiculously toxic it is also very long acting.
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Riemann Zeta
Bluelighter
Ah, methyl-phenylpiperazinepropioate (MPPP), one of the biggest, saddest and most tragic fuck-ups in organic chemistry history. A demonstration of why it best to stick to the morphine-esque compounds for your opioid pleasure.
fastandbulbous
Bluelight Crew
^^
Assume you meajnt piperisine, not piperazine, but yes, one short cut (substituting salt/ice bath for dry ice/acetone) in it's synth and you end up with MPTP and the best (if that's the right word) way to cause Parkinsons disease known.
Actually, out of the fentanyl derivatives, I included the last one (alpha-methyl carfentanyl) as a possible "you'll never believe it" potency compound. If the step from fentanyl to alpha-methyl fentanyl results in a 10-fold increase in potency, it's possible that alpha-methyl carfentanyl may have a dose range in the nanogram dose range - that's just taking the piss in terms of potency compared with morphine!
PS. Has anybody noticed that carfentanyl is technically an alpha-amino acid derivative (although it'll not be an optical isomer due to the symmetry of the piperidine ring)
Assume you meajnt piperisine, not piperazine, but yes, one short cut (substituting salt/ice bath for dry ice/acetone) in it's synth and you end up with MPTP and the best (if that's the right word) way to cause Parkinsons disease known.
Actually, out of the fentanyl derivatives, I included the last one (alpha-methyl carfentanyl) as a possible "you'll never believe it" potency compound. If the step from fentanyl to alpha-methyl fentanyl results in a 10-fold increase in potency, it's possible that alpha-methyl carfentanyl may have a dose range in the nanogram dose range - that's just taking the piss in terms of potency compared with morphine!
PS. Has anybody noticed that carfentanyl is technically an alpha-amino acid derivative (although it'll not be an optical isomer due to the symmetry of the piperidine ring)
rachamim18
Bluelighter
MPPP and MPTP...
MPPP is an analog of Meperidine [Demerol]. The effect is more pronounced in that the subjective effects are indiscernible from heroin. MPTP is, as Fast pointed out, MPPP with a simple mistake. The substance was sold in California as heroin in the early 80s [actually there were two seperate instances of it]. Those that injected it all developed Parkinsonian disorders. If you are really curious try digging up a copy of the "Nova" episode on the substance and its effects. It is one of the better [evenhanded] pieces I have seen on "drug scare stories."
MPPP is an analog of Meperidine [Demerol]. The effect is more pronounced in that the subjective effects are indiscernible from heroin. MPTP is, as Fast pointed out, MPPP with a simple mistake. The substance was sold in California as heroin in the early 80s [actually there were two seperate instances of it]. Those that injected it all developed Parkinsonian disorders. If you are really curious try digging up a copy of the "Nova" episode on the substance and its effects. It is one of the better [evenhanded] pieces I have seen on "drug scare stories."
rachamim18
Bluelighter
Still around...
I have not seen MPPP since 92 but it is always possible [if not probable] and I hope to G-D that I never hear of MPTP on the street again.
I have not seen MPPP since 92 but it is always possible [if not probable] and I hope to G-D that I never hear of MPTP on the street again.
fastandbulbous
Bluelight Crew
PEPTP
Somebody in another thread was aking about PEPAP, as there was some to be had via illicit sources. Thing is, any of the pethedine reverse ester compounds (the ones based on MPPP - in that instead of a carboxylic acid group attached to the 4 position, there is an hydroxyl group) are all capable of producing an xxxTP compound (tetrahydropydridine), when instead of undergoing esterification to the desired product, instead undergo an elimination reaction (it's quite common for tertiary alcohols to do this).
I've seen no info stating that PEPTP is a Parkinsons causing agent, but the toxicity of MPTP is bacause it is metabolized to 1-methyl-4-phenylpyridinium ion. Replace methyl with phenethyl, and you'll still get a pyridinium ion, and that sound a tad dodgy. It's a fault inherent in the synthesis of any prodine (pethedine reverse ester) drug, and considering the lack of quality control in illict drug manufacture, along with the high potency of the prodine series of drugs, it's still an accident waiting to happen.
Somebody in another thread was aking about PEPAP, as there was some to be had via illicit sources. Thing is, any of the pethedine reverse ester compounds (the ones based on MPPP - in that instead of a carboxylic acid group attached to the 4 position, there is an hydroxyl group) are all capable of producing an xxxTP compound (tetrahydropydridine), when instead of undergoing esterification to the desired product, instead undergo an elimination reaction (it's quite common for tertiary alcohols to do this).
I've seen no info stating that PEPTP is a Parkinsons causing agent, but the toxicity of MPTP is bacause it is metabolized to 1-methyl-4-phenylpyridinium ion. Replace methyl with phenethyl, and you'll still get a pyridinium ion, and that sound a tad dodgy. It's a fault inherent in the synthesis of any prodine (pethedine reverse ester) drug, and considering the lack of quality control in illict drug manufacture, along with the high potency of the prodine series of drugs, it's still an accident waiting to happen.
rachamim18
Bluelighter
PEPAP,etc...
Fast: What do you think about PEPAP/MPPP's inhibition of CYP2D6, as in potentiating CYP2D6 substrate substances [methamphetamine among them]?
Fast: What do you think about PEPAP/MPPP's inhibition of CYP2D6, as in potentiating CYP2D6 substrate substances [methamphetamine among them]?
fastandbulbous
Bluelight Crew
Didn't know they did. Still wouldn't touch them with a barge pole though, purely because of the Parkinsons link.
rachamim18
Bluelighter
Touching them...
I am in agreement with the only exception being if I had some control over the supply. As for the potentiating qualities, I wouldn't find it a benefit as I am not much up for stimulants...I just had a thought: what is it that has that reaction on the substrates...I've read the 2 papers [that I know of] on it and understand the effect but not the cause. The researchers haven't pinned it either but I'm puzzled as to why them and not Meperidine.
I am in agreement with the only exception being if I had some control over the supply. As for the potentiating qualities, I wouldn't find it a benefit as I am not much up for stimulants...I just had a thought: what is it that has that reaction on the substrates...I've read the 2 papers [that I know of] on it and understand the effect but not the cause. The researchers haven't pinned it either but I'm puzzled as to why them and not Meperidine.
Hessel R.K.
Bluelighter
not to beat the thread into the ground, sphinx, but how the fuck would you get out of a hazard suit contaminated with that shit? You would never know if you has washed it all off, touch your eye sometime later, and have od a million times.
joystick
Bluelighter
Future Pain Relievers
There are tons of synthetic, semi-synthetic and natural opioid drugs out there. As far as potency, the fentanyl family is hard to beat, but overall, the all-natural morphine, and heroin one of its semi-synthetic derivatives, are probably not going away anytime soon. To obtain morphine, all one has to do is extract it from poppy organic matter. Heroin can be made from morphine in one step using acetic anhydride. Aspirin and ibuprofen are also good pain relievers, though not addictive, and will probably still be used in the future.
The only exciting, new, and probably addictive pain reliever being tested right now that I know of is Abbott laboratories' ABT-594 (chemically, 5-(2-azetidinylmethoxy)-2-chloropyridine. Not only is ABT-594 200x more potent than morphine as an analgesic in animal models, but it releases DA and NE (a la methamphetamine) and is a nicotinic receptor agonist (a la nicotine). Also, its action is not blocked by the co-administration of opiate antagonists such as naloxone or naltrexone. ABT-594 sounds promising, to say the least, in my opinion. Time will, hopefully, tell.
There are tons of synthetic, semi-synthetic and natural opioid drugs out there. As far as potency, the fentanyl family is hard to beat, but overall, the all-natural morphine, and heroin one of its semi-synthetic derivatives, are probably not going away anytime soon. To obtain morphine, all one has to do is extract it from poppy organic matter. Heroin can be made from morphine in one step using acetic anhydride. Aspirin and ibuprofen are also good pain relievers, though not addictive, and will probably still be used in the future.
The only exciting, new, and probably addictive pain reliever being tested right now that I know of is Abbott laboratories' ABT-594 (chemically, 5-(2-azetidinylmethoxy)-2-chloropyridine. Not only is ABT-594 200x more potent than morphine as an analgesic in animal models, but it releases DA and NE (a la methamphetamine) and is a nicotinic receptor agonist (a la nicotine). Also, its action is not blocked by the co-administration of opiate antagonists such as naloxone or naltrexone. ABT-594 sounds promising, to say the least, in my opinion. Time will, hopefully, tell.
So does nicotine release dopamine and norephedrine. You may not notice this but it is in fact the case. That is why cigarette smoking is so addictive, IMO. The one thing epibatidine, nicotine & ABT594 do not touch is serotonin. If this drug finally does get mass-produced i'll be there at my doctors surgery asking for a script. The cyclobutamine ring is fascinating. It is not just put there because it looks pretty either, it confers extreme potency increase over the perhaps more natural pyrollidine 5-membered ring compounds in SAR studies.
blase deviant
Bluelighter
- Joined
- May 9, 2004
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No offense, but all the carfentanyl stuff seems like dicksizing. IMO, it's not the potency, it's the subjective effects.
I'd rather take a 500mg of a drug if it gave me a better buzz as compared to a similar drug active at .00000005mg. Factoring in cost, etc...
E.x. heroin is less potent than fentanyl, but I've heard people say they don't like fentanyl.
Personally a drug I'd love to try but probably never will is levorphanol/levomethorphanol (I forget what the longer, pre-metabolization drug is called, but you all know what I mean).
I'd rather take a 500mg of a drug if it gave me a better buzz as compared to a similar drug active at .00000005mg. Factoring in cost, etc...
E.x. heroin is less potent than fentanyl, but I've heard people say they don't like fentanyl.
Personally a drug I'd love to try but probably never will is levorphanol/levomethorphanol (I forget what the longer, pre-metabolization drug is called, but you all know what I mean).