N&PD Moderators: Skorpio
2'-Hydroxycocaine...
Holy_cow
Bluelighter
was 10-fold more potent than cocaine and equipotent to WIN-35428. 3'-Hydoxycocaine was 4.75 times less potent than cocaine, and 4'-hydroxycocaine was 1.5-fold more potent than cocaine. 2'-Acetoxycocaine was 3.58-fold more potent than cocaine. This pertains to IC50 values, so might not necessarily translate to in vivo potency. J. Med. Chem. 1997, 40, 2474-2481.
fastandbulbous
Bluelight Crew
2'-hydroxycocaine doesn't really tell you where the hydroxyl group is situated - is it the tropane ring or the benzoyl group that has the substitution. Also, in terms of potency, do the IC50 figures pertain to DAT inhibition as that's not the only transporter that cocaine inhibits?
LuxEtVeritas
Bluelighter
yeah probably for DAT as IC50
mushi mushi 88
Bluelighter
Wait a minute are you telling me that there is a drug more potent than cocaine...?
How come this stuff isn't on the street? It would take off...!
LuxEtVeritas
Bluelighter
uh, there are dozens of drugs in the same class that are FAR more potent than cocaine and/or more overall pleasing ands/or less toxic
mushi mushi 88
Bluelighter
Are they legal in any way or just no way?
fastandbulbous
Bluelight Crew
^It's an ester of ecognine (cocaine is methyl benzoyl ecognine) and as such covered by the misuse of drugs act
Iodjini_dk
Bluelighter
Is it because they are hard and/or expensive to synthesize then? If they're as difficult to purify and synthesize as cocaine I can see why, but as mushi says these drugs would probably have a surge in popularity if they entered the market.
mushi mushi 88
Bluelighter
Send some to Australia I'm sure their would not be much of a price difference over this way because coke already cost so much...
If this stuff was over here some people could be making some serious dough... Would it be detectable through customs and the test they do to determine the purity would it show up as cocaine or something different or not at all...?
Débora Lima
Greenlighter
But this drug is new there are no analytical methods developed for hydroxycocaine, regardless of where the hydroxy group is 2'-or 3'- or 4'- position of aromatic ring.
But the synthesis of 2'-hydroxycocaine is very complicated, and there are neither analytical standard to buy. I do not know how these users do use. Anyone know ??
dopamimetic
Bluelighter
There was this reverse ester cocaine that a (previously serious) vendor claimed to have synthed. Turned out then that it was amfepramone and phenacetin and either they have been scammed themselves - and did not care to make a single analysis of a novel chem, or they intended to scam.
I know about these cocaine relatives, some are even on wikipedia- and wondered too why no one has been available at least as far as I know. Even if the synthesis goes over cocaine, this could be done in some countries where probably the other reagents aren't too hard to acquire either and with some being much more potent, and legal in many countries, it would make sense economically to do so.
just because somethings more potent doesnt mean ur gonna feel 10 x better on it. There are opiates thousands of times stronger than heroin but heroins so dangerous because it feels so good and acts in a unique way. Just cuz a substance hits the same receptors better doesnt mean ur necessarily gonna like it more
To confirm, it is on the benzoyl group. It was x10 more potent in isolated cells if I recall, the -OH will lower the cLogP so it wouldn't accumulate in the brain as well. Maybe an activating route that is more lipophilic would be worth investigation... presuming you an get hold of ecgonine methyl ester....
dopamimetic
Bluelighter
Yeah, but that does not mean that the opposite has to be true as well, imo. Butyr-fentanyl as an example has been a quite nice substance (albeit too potent for one to feel safe handling it).
I just mean if one could turn coca leaves into some 10x as potent coca analogue which feels roughly like original cocaine or even, say, lasts slightly longer - there would also be much more profit in it. And it would be legal in many countries.
Edit: And if the structure is changed enough eventually to not to light up in drug tests, well.. another plus. I guess (but could be wrong) that Nocaine for example would not show.
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adder
Bluelighter
I thought that in case of reuptake inhibitors IC50 tells more about the potency of effects than Ki. A drug may have a high affinity towards DAT, but if IC50 is much higher, then the drug will be relatively weak. Or did I get it wrong?
serotonin2A
Bluelighter
Ultimately IC50 is more important because that directly measures the response to the drug. Binding to DAT is one aspect of their action, but there are multiple binding sites on DAT, and there can be multiple mechanisms that lead to the inhibition of dopamine uptake. However, even the IC50 does not tell the entire story because the rate of brain penetration also plays an important role in the response to DAT inhibitors.
doppelgänger1
Bluelighter
Ki is calculated from IC50
serotonin2A
Bluelighter
There are two different IC50 values that would come into play: (1) IC50 for binding to DAT (measured by displacing the binding of another ligand), which is used to calculate the Ki for binding to DAT; and (2) the IC50 for inhibiting dopamine uptake. The two IC50 values are not equivalent. We were previously discussing the IC50 for dopamine uptake, not the IC50 for inhibiting binding to the transporter protein.