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Once and for all: Dextroamphetamine vs. dextromethamphetamine

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sort of makes me wonder why some of these things are so beloeved. Maybe I'm misunderstanding this, but based on the numbers, oughtn't mazindol be way more enjoyable than cocaine, or at least much more potent?
 
Ham-milton said:
sort of makes me wonder why some of these things are so beloeved. Maybe I'm misunderstanding this, but based on the numbers, oughtn't mazindol be way more enjoyable than cocaine, or at least much more potent?

I remember hearing that before it was taken off the market that some narcoleptics were presribed mazindol. Essentially that was the only thing that worked for them.

I am wishing that the folks who made this chart would have added methylphenidate, methaminorex, L-amp, and PEA.
 
what's with

the cocaine numbers, they look like dead releasers across the board, and their reuptake inhibition numbers are in the like half a micromolar range?
 
Ham-milton said:
sort of makes me wonder why some of these things are so beloeved. Maybe I'm misunderstanding this, but based on the numbers, oughtn't mazindol be way more enjoyable than cocaine, or at least much more potent?

those numbers tell a very small part of the story, mazindol is potent but slow onset and long duration. there are indications that it also does not bind to the same site as cocaine.
the figures for locomotor activity versus extracellular dopamine do not correlate for a lot of stimulants, so there is much complexity, DAT is not dat.
 
I've tried mazindol before (both low and high doses)--definitely nothing to write home about. It is certainly very "clean" feeling, but not particularly stimulating. Those expecting a methylphenidate-like experience and focusing effect would be disappointed. I'm not sure why it would have been taken off the market.

Anyway, there is more to DAT binding than just Ki, it appears that different classes of DAT inhibitors induce different conformational changes at the DAT and hare differing behavioral effects; some DAT inhibitors are completely devoid of stimulant activity.
 
rae26 said:
...does this mean that such low amounts are below the threshold of neurotoxicity; possibly even that of serotonergic-induced neurotoxicity?

not necessarily. "toxic" drugs are prescribed regularly if the benefits outweigh the possible risks, and if i remember right the dr has to (well, supposed to) inform the patient of all the possible risks and why he thinks this 'toxic' medicine will help better than a less toxic alternative, and the pt always has the option of getting something else instead
 
The question of desoxyn (meth) being in the clinic for narcolepsy is that it MUST come on quicker (methylated being more lipid soluble) and last longer (better protected from MAO) than AMP. You can take AMP and wait the 15-20 mins or so to make it to work or school, but when you are narcoleptic and you feel an attack coming on when driving in heavy traffic and can't easily pull off the road for a nap, a quick acting jolt that will last awhile and be strong enough, is what you need.

Eh, that seems like a completely superfluous theory as it would be just as easy to produce a dexamphetamine sublingual tabletor nasal spray if speed of onset was that important. Considering that given a slightly higher dose, dexamphetamine is just as decent a locomotor stimulant, only it doesn't have the euphoria of d-methamphetamine.

On top of everything else, sec amines are more basic than primary and increasing polarity of a molecule, as a rule, reduces lipid solubility unless it's a long chain alkyl group that can form a micelle like structure


My biggest concern is that such dopaminergic compounds as AMP and meth, are structurally related to MPTP.

Other than containing an aromatic ring and an amino function, they're not that much like each other. Amphetamines are at their core a Ph-C-C-N and unconstrained, This is vastly different to the Ph-C-C-C-N of MPTP, which is conformationally restrained due to the heterocyclic ring. Add to this the ease with which the piperidine ring is easily converted to a stable aromatic pyridinium species by MAO-B compared with the elimination of the amino/methylamino group in amphetamine/meth and there's very little they have in common.

I've certainly never heard of dextroamphetamine being a carcinogen.

The secondary amine of meth can undergo a reaction with nitrites found in meat preservatives to produce a nitrosoamine; under the same conditions a primary amine like amphetamine is converted to an alcohol, which isn't toxic (tertiary amines are unreactive in the presence of nitrites). Now nitrosoamines are well known to be carginogenic, which is yet another black mark against methamphetamine.

Finally, methampheamine exerts it's neurotoxic effects due to the depletion of neurotransmitters dopamine & 5HT from the neurones. Eventually this leads to a situation where 5HT neurone will take up synaptic dopamine & this is what buggers them rather than some quaternary aromatic compound like MPP+

PS Much more unpleasant, (neuro)toxic drugs are used every day to treat a variety of conditions, it's a risk benefit assessment. You only have to look at something like the vinca alkaloid, vincristine for a really nasty example. Here's a much bigger list of neurotoxic toxic drugs that have acceptable risk factor considering what they're used for treating
 
fastandbulbous said:
Finally, methampheamine exerts it's neurotoxic effects due to the depletion of neurotransmitters dopamine & 5HT from the neurones. Eventually this leads to a situation where 5HT neurone will take up synaptic dopamine & this is what buggers them rather than some quaternary aromatic compound like MPP+
But would 'depletion' even occur at therapeutic or low therapeutic doses? I know that there have been made several studies into methamphetamine neurotoxicity but most don't even seem to account for plasma concentrations lower than ~80 ng/mL, if they at all include concentration as a variable.

And still I'm wondering why Desoxyn is so hyped (see here for example) if its pharmacokinetic effects are essentially the same as Dexedrine at an equivalent dosage. If 20-25 mg's a day is below the threshold for serotonergic activity, then I guess we could rule that out as the deciding factor?
 
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Here is the text I found years ago. Too bad I cannot remember what it came out of. I think it is an old pathophysiology book.

carc.jpg


It is stating that amp sulfates cause leukemia. 8(

If true you think this would have killed Paul Erdos instead of what did.
 
Well I'll be jiggered. I guess I was wrong. Still, considering the vast myriad of carcinogens/mutagens out there (air & water pollution, smoke, cooked food, UV light, aromatic pesticides, alkyl halides, viruses, etc...), I think the risk of developing cancer solely from clinical doses (<100mg/day) of dextroamphetamine is fairly remote. It may be another brick in the wall, but I doubt it is all that significant.
 
I've been doing methamphetamine every weekend for the last three weekends, and after reading this thread I'm starting to worry a bit about my health. Until now I had considered the reported neurotoxic effects of methamphetamine to be hyped like the neurotoxic effects of most illicit drugs are. But this thread has certainly changed my mind. The doses I'm using are about 20-30 mg initially and redosing once or twice with the same amount, rarely exceeding 80 mg and never missing more than 36 hours of sleep. To what extent would this cause neurotoxicity repeated three weekends in a row, would you think?

I'm wondering if someone knows of any human studies of methamphetamine toxicity where non-drug users are given therapeutic doses of methamphetamine and various indicators of neurotoxicity are recorded before and after. It seems this would provide a clearer picture of the degree of methamphetamine toxicity in humans at reasonable doses.
 
Anyone have EC50 values for MPH?

I've always prefered d-amphetamine to methamphetamine. Maybe its the high values for NE release that result in the intense focus not seen in methamphetamine...
 
^--That's a good question.

I don't have the EC50 value for MPH, but I find MPH just as good as AMP, so I bet they have similar values. (The dex form is even better.) METH is stronger still, but somehow, I think I also prefer the first two to the latter, which lasts too long--making sleep impossible--and sometimes comes with toxic impurities (from the P/HI route).

Maybe a better title for this thread would be "Once and for all: Dextroamphetamine vs. dextromethamphetamine vs. dexmethylphenidate." I think they're all good.

Provigil and Strattera are not even in the race for the title of all round best stimulant, that's for sure, and cocaine is in a class by itself (the tropanes).
 
I am very curious about methylphenidate's NE/DA uptake ratio, but for whatever reason, I can't seem to find the data. I am also interested to know what mphs's ec50 values are for 5-HT uptake. Anyone?

For whatever reason, I find the comedown of d-methylphenidate beneficial, in terms of creativity...
 
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I very much prefer methamphetamine's lower ratio of adrenergic stimulation, and increased central/decreased peripheral effect compared to the already-pretty-clean-for-most-folks d-amph. Too bad the serotonin release affinity is a concern.

Because, if not for that, as in dextroamphetamine I don't think neurotoxicity specifically from the molecule, besides behaviorally-mediated toxicity and perhaps glutamatergic excess, would be a major concern at anywhere near therapeutic or even moderate recreational doses, studies showing plastic changes in DAT transporters (like, duh) aside.

(bump)
 
>>Are there any actual differences in CNS stimulant effects between dextroamphetamine (Dexedrine) and dextromethamphetamine (Desoxyn), except for the increased potency per mg of meth (due to increased lipid solubility)? Is it true that Desoxyn gives clearer thoughts and more "control" and at the same time less side effects or is that just placebo?
>>

IIRC, d-meth has a higher ratio of dopaminergic to norepinephrinergic effects than d-amp. Also, since meth more readily crosses the BBB, it has a higher ratio of central to peripheral effects than its competitors.
...
From what I've heard, many people indeed prefer meth, for its smoothness and "strength". I think that the widespread preference for d-amp's effects is due to differences of routes of administration. Meth is more often taken through quick-acting methods and repeatedly, leading to a rougher, more anxious high. People are more apt to eat single doses of d-amp.

ebola
 
Would anyone care to go into more detail about the structural changes to DAT after dextroamphetamine usage. And the implications for behavioral changes or impairment. Do we even know at what dosages these changes begin to manifest yet?

Or at least a link pointing to a discussion on the subject?
 
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