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Psuedoephedrine Vs. Methamphetamine psychoactivity

nuke

Bluelighter
Joined
Nov 7, 2004
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I got in a discussion with a tweaker friend last night over whether pseudoephedrine could be classified as a type of "speed" or not (since other slightly irrelevant chemicals like methylphenidate are often grouped into this too). He said that only amphetamine derivatives with heavy dopaminergic effects should really be classified as speed (d-amp, methamp, and amp for the most part).

Anyway, this discussion got me curious about the structure of these chemicals. Looking them up, I saw the only differences between methamphetamine and pseudoephedrine are the swapped positions of the NH-CH3 and CH3 from the second extended carbon, and the partially oxidized first extended carbon in PE (which is hydrogenized in methamphetamine).

My question is, how do these small changes in structure yield such different psychoactivity (or more generally: how does methamphetamine work opposed to pseudoephedrine in the brain, and why?)?
 
Mainly because pseudoephedrine has poor lipid solubility and hence doesn't get into the brain very well.

Also, its more selective for noradrenaline release as can been seen from this figure, robbed from Rothman et al., 2001
PEA-EC50size.gif
 
From memory pseudoephedrine behaves almost exactly like amphetamine.... if it gets to the brain. It's got poor lipid solubility, as mentioned, and so it doesn't :p
 
Direct vs indirect

If I remember correctly, ephedrine also has some direct effect on some of the adrenergic receptors (I think it's one of the beta adrenergic receptors), whereas with the amphetamines it's all indirect activity (by causing cathecolamine release).


Also, according to the above table, (+)-norpseudoephedrine isn't far behind (-)-cathinone in terms of activity w.r.t. cathecolamine release, yet everything I've read ascribes the activity of khat (Catha edulis) purely to cathinone, stating that a few days after harvesting, by which time the cathinone has been converted to norpseudoephedrine, the plant has lost its CNS stimulant properties; looking at the figures again, I'm having difficulties understanding why
 
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direct agonist activity of pseudoephedrine

got a ref for that fastandbulbous?
because that would be interesting
what adrenergic receptor?

let me look at some structures of say... phenylephrine (a1 agonist) vs pseudoephedrine...
http://www.elmhurst.edu/~chm/vchembook/663adrenergic2.html

the difference appears to be a hydroxylation of the benzene ring in phenylephrine that isnt present in pseudoephedrine, and of course the alpha methyl group in pseudo that phenylephrine doesnt have

adrenaline has a two hydroxyl groups on the benzene ring, and noradrenaline is lacking the N-methyl group

this site also has a (crappy) receptor site interaction diagram

not that this really actually proves anything, but i would like to see the reference....
 
He's right, but I'm not so sure about relavence...

check out here and here... ctrl-f and search for ephedrine... the links are refernced...
 
undegrad pharmacology texts

I have Rang Dale Ritter & Moore "Pharmacology"
It seems to be pretty common. As far as a really broad spectrum book about the effects of drugs on physiological systems, i'd give it about an 8/10.
It has a section on neurotransmission, which is OK (6.9-7.1/10) but if you're into your neuro Rang et al. doesn't cut it. I'm considering selling it, actually.
It's pretty good for systematic pharmacology. As far as introducing heavy pharmacological theory and molecular pharmacology, such as receptor-ligand interactions, signalling, receptor trafficking etc., it's crap.

Another one is Katsung et al. "Basic & Clinical Pharmacology" which is obviously more clinically oriented. I havent looked at it too much but if you have a clinical bent (i don't) it might be worth checking out.

BilZ0r can probably reccomend some psychopharmacology texts - that's not really my area

Depending what you're after (if you like neuro,) you might want to consider getting Kandel, Schwartz and Jessel - "Principles of Neural Science"
it's the undergrad neuro bible :)
 
Actually I've got Essential Psychopharmacology (Stephen M Stahl) from Cambridge University Press, and it's quite a good psychopharmacology text book (it's also not much bigger than A5, so it's not this unwieldy affair like Rang Dale Ritter & Moore ) and somebody obviuosly had fun doing the illustrations inside. It's definitly worth a look if you want a good grounding in psychopharmacology.
 
I am not really that garbaged with pharmacology at the mo. Definately interested in learning more about this Rothman guy though. Enzyme assays are 'da bomb!
 
Methcathinone actually looks like a better stimulant, since the NE/DA levels are closer, rather than NE being a lot higher. So why does everyone do meth(amp)?

Is there anything that affects DA a lot more than NE (or no NE), and doesn't/barely touches 5HT?
 
You're forgetting pharmacokinetics blase... Cathinones have a high peripheral/brain fraction.. so they cause more unpleasant body effects.
 
psychostims and peripherally selective B-blockers

bilZ0r and I were actually having a conversation about this on IRC quite a while ago. I ended up obtaining some atenolol a while ago, but I gave it to a friend (25mg) who was on a whole bunch of speed and sweating like a pig.

i was talking to a friend who reckons that if you start blocking the effects of catecholamines at adrenergic receptors that they'll start binding to other receptors which they also have affinity for and you get a whole plethora of side effects.

has anyone actually *tried* this (or know an uncle's plumber that has..)?
anyone got any ideas as to what the next highest receptor specificity of noradrenaline down from adrenergic R's is?

ah, i'm working at the lab at the moment so don't really have time to do the searches sorry, but I just thought i'd chuck the idea out there.
 
a) yes I have heard of it working in both cannabis and meth, though better for cannabis..

b)Your friend who said "if you start blocking the effects of catecholamines at adrenergic receptors that they'll start binding to other receptors" this is crazy, think about it...

In order for a drug to have a significant effect on a receptor, is concentration has to start getting up around its Kd for that receptor... i.e. higher concentration leads to higher binding... This secondary receptor doesn't care wither adrenergic receptors are being bound to or not, all it cares about is the concentration of the drug

And do you think blocking adrenergic receptors will have much effect on the concentration of amphetamine in your body? No, not at all... EVEN IF amphetamine bound to adrenergic receptors with any affinity, the increase in plasma amphetamine would be microscopic... You're blocking the action of the adrenaline and noradrenaline (and maybe dopamine) that is peripherally released, not the amphetamine...
 
No, I was meaning, it can decrease the peripheral effects of cannabis, i.e. heart racing.
 
it would be interesting to find out what are the subjective effects of a non-peripherally specific B-blocker (eg propranolol) combined with a decent dose of cannabis.
potentialyl, it could be basically the opposite of smoking cannabis on amphetamines (nasty, IMHO)

damn myelin is taking up all my diaminobenzidine stain...
my purkinje cells are still coming up nicely through the background though. (staining cerebellar sections with some different huntingtin antibodies for use as a positive control)

/me goes back to the microscope....
 
How many times are you gonna drop that you're in a lab? lol
 
this may be a little off topic, but it always confused me...

about 2 or 3 years ago, I and a friend were both bored and looking for a cheap legal high because we were strung out on coke, no connections at the time, and weed was just not doing the trick.

I came up with the idea (thank you internet) to buy a pound of raw ephedra plant material from an herb shop and extract the ephedrine into a tea along with some yohimbe bark and drink it for the good old fuck of it.

So when it arrived, we boiled some water, threw in a small amount of alcohol and a large amount of ephedra with a smaller amount of yohimbe. (nothing exact really.) Neither one of us expected this to work of course and proceeded to boil for a short time and pour it all through a basic strainer to remove the plants and leave a dark brown tea.

We both drank about 12 to 14 ounces of the stuff on a sunday afternoon. About 4 or 5 pm.

About 30 mins later my friend is throwing up with a sick stomach, but I feel fine. Then we go to smoke some weed and I realize I don't feel stoned. I'm speeding. We both at this point start driving around just talking stupid shit.. you know the deal.. and while it wasn't all that euphoric we were both very spun.

Now yohimbe is supposed to just be an old aphrodisiac and ephedrine isn't supposed to be intense at all right?

Needless to say, I went home that night and tried to sleep and tossed and turned and eventually came down only to watch the sun rise out my window.

It's 5:30am and I have work in an hour and I've just missed a night of sleep testing out some silly mormon tea recipe.

So what confused me is... why was the ephedrine so strong when taken in this manner? It felt very close to methamphetamine but not nearly as up to the moon euphoric.

Taking simple ephedrine pills doesn't even compare to the high however. The tea was very calm and focused not all jittery and stressed out like when you eat ephedrine pills.

Had all the tell tale signs of a meth high, such as, meth dick, sweaty palms, cold chills, tingly hair, racing heart, tight jaw, etc...

Haven't done that again to this day but... it was interesting how well it worked. Any ideas why it worked so good, as opposed to ephedrine pills which just make you feel like shit?
 
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