Abuse Potential of Ephedrine Isomers

[Ham-milton]

I was looking for information about the actual abuse potential of pseudoephedrine after some moron was comparing it to cocaine in OD (after snorting a tablet 8) )

I'm assuming that they only used 6 monkeys in total for this study; I'm not sure how many monkeys they typically use for these sorts of things. That might be a bit small. Then again, how many monkeys do you turn into jonkeys? (get it? 8) )

10-33x less potent would put this in a dosing range 2.5-8.2g assuming a quarter gram of cocaine for recreational purposed. I'd like to know how much they were actually using on a mg/kg basis. That seems awfully high though. I found a site saying 1.2g was a fatal dose and just adjusted downward. I have very limited cocaine experience.

Wouldn't the required dose make it toxic for monkeys? That would be a shitload for a human.

Document title
Reinforcing effect of pseudoephedrine isomers and the mechanism of action
Authors
WEE Sunmee (1) ; ORDWAY Gregory A. (1) ; WOOLVERTON William L. (1) ;
Authors' Affiliations
(1) Department of Psychiatry and Pharmacology, University of Mississippi Medical Center, Jackson, MS 39216-4505, ETATS-UNIS
Abstract
It has been proposed that ephedrine and its isomers may have abuse potential. When made available to rhesus monkeys (n 4) for self-administration, (+)-pseudoephedrine functioned as a positive reinforcer in all monkeys, as did (-)-pseudoephedrine in two of three monkeys. Pseudoephedrine isomers were 10- to 33-fold less potent than cocaine. In in vitro binding in monkey brain tissue, both isomers had low affinity for dopamine and serotonin transporters by at least 200-fold relative to cocaine, but comparable affinity for norepinephrine transporters. (+)-Pseudoephedrine also blocked dopamine uptake in 293 hDAT cells with low potency relative to cocaine. When given in vivo (+)-pseudoephedrine significantly displaced radioligand binding to dopamine transporters with a potency comparable to that in self-administration. Therefore, pseudoephedrine isomers can function as reinforcers and the mechanism at dopamine transporters may underlie this effect. However, pseudoephedrine appears to be a weak reinforcer and may have relatively low abuse potential.

All of these different ephedrine are a little confusing to me, but in this case, the +/- is the difference in rotation of the alpha methyl group, right? Then the difference between pseudo and ephedrine is the rotation of the beta hydroxy, right?

 

[toxide]

pseudoephedrine is another way of say ephedrine isomer(+ or -)i assume when he refers to pseudoephedrine as a whole he really means ephedrine(+&-) atleast that was my understanding. but in anycase... all this data seems like old news, who doesn't know all that? very minimum DA fx and lots of adrenaline FX ie-no abuse potential really

 

[immaturepoop]

(+/-) involves the relative stereochemistry of the molecule, whereas (R/S) involves the absolute stereochemistry of the molecule (at the chiral centers). (+) and (-) determines the rotation of plane polarized light (dextro and levo) and (R - clockwise) and (S - counterclockwise) determine the rotation relative to the priority of the substituents of the chiral carbon.

 

[MurphyClox]

(+/-) involves the relative stereochemistry of the molecule, whereas (R/S) involves the absolute stereochemistry of the molecule (at the chiral centers). (+) and (-) determines the rotation of plane polarized light (dextro and levo) and (R - clockwise) and (S - counterclockwise) determine the rotation relative to the priority of the substituents of the chiral carbon.

Exactly! What's left? ...
(-)-(1R, 2R)-Pseudoephedrine = L-Pseudoephedrine
(+)-(1S, 2S)-Pseudoephedrine = D-Pseudoephedrine

 

[Ham-milton]

Right, there's two isomers of Pseudoephedrine, two for Ephedrine, so really there's four for ephedrine.

With the two ephedrine (proper) isomers, I don't believe there is any self administration; I believe this is limited to the two pseudoephedrine isomers (one really).

Does the lack of potency, though, make it an impractical drug of abuse? It seems odd that something that's reinforcing for monkeys hasn't turned up in humans.

That makes sense.

Has similar research been done with PPA? I'm assuming that only Cathine is reinforcing in that family.

 

[immaturepoop]

^ an easy way to find out how many stereoisomers of a compound exist is to take the number of stereocenters in the molecule and put in for n using the formula (2^n). Yes, 4 isomers exist for ephedrine because there are two stereocenters which gives a total of 4 isomers.

 

[MurphyClox]

Does the lack of potency, though, make it an impractical drug of abuse? It seems odd that something that's reinforcing for monkeys hasn't turned up in humans.

From personal experience, I wouldn't say that it [=Pseudo-E] doesn't have any potency. Effects are more subtle somehow but definitively present! It is IMO a drug of abuse...for plp who like the constant, light turn-on.

 

[nuke]

120-240mg of pseudoephedrine (racemate) is a dose that's centrally acting to me, duration about 2-4 hours, however peripherally it's not very fun and I wouldn't recommend it.

The LD50 must be up there because I once had a friend who took 600mg pseudoephedrine, 120mg ephedrine, and 100mg methamphetamine and he was fine afterwards (was acting pretty weird though).

 

[The_Idler]

for fucks sake that's a good decongestant.

they're getting rid of it and replacing it with the completely inactive phenylephrine.

 

[MurphyClox]

I once had a friend who took 600mg pseudoephedrine, 120mg ephedrine, and 100mg methamphetamine and he was fine afterwards (was acting pretty weird though).

Indeed? what a surprise...

 

[Ham-milton]

Wow, no kidding. I would have thought a combination like that would have left irrepairable cardio damage.

Anything more than 50mg of ephedrine leaves me feel like horrible shit. Double that, high dose amphetamine and massive pseudoephedrine? Ick.

 

[nuke]

That was about 4 or 5 years ago, the same guy had a chest CT scan two years back and he appears to have moderate cardiac fibrosis but he's also been a methamphetamine abuser for about 12 years. Tolerance may have played some part in his survival.

I saw another girl who IV'd an estimated 500mg of methamphetamine and 250mg of MDMA in a suicide attempt -- coma for a over a day then survived but with pretty substantial chronic cognitive deficits and psychiatric problems. Her cardiac symptoms were stable upon release. She hasn't been able to return to school or work since the ordeal.

 

[Paregoric Kid]

sure ephedrine can be abused and be self administered by monkeys, but so can bupropion. though I guess it could be that ephedrine penetrates the BBB of monkeys more efficiently than in humans and that monkeys find it to be more like amphetamine than humans do.

 

[vecktor]

junky munkys are weird in their choices, in studies they choose procaine over cocaine.
so them liking ephedrine as well as methedrine is no surprise.

 

[butane]

It's interesting that some people get stimulating effects from pseudoephedrine while others don't. I feel absolutely nothing from it in the way of stimulation, only decongestion.

 

[<pyridinyl_30>]

I prepared and drank some ma huang tea one time, and I was fairlly strongly intoxicated afterwards, but it was rather unpleasant and I didn't do it again. I obviously don't know how many milligrams of ephedrine it was that I drank, though.

I've often wondered about the possibility of psychoactivity of
benzyl-methoxymethamphetamine. Anybody ever run across some research relating to this compound, which could be easily made in one step from ephedrine?

 

[Ham-milton]

where is the benzyl and methoxy located??

 

[<pyridinyl_30>]

In IUPAC I mean 1-methoxy-2-methylamino-1-phenylpropane, which has a total of 4 possible stereoisomers.