Posted by chemist on June 30, 2004, at 20:19:32
In reply to Re: Sounds like a question for CHEMIST. Desoxyn, posted by paulbwell on June 28, 2004, at 22:51:39
> > > > Assuming Desoxyn is "neurotoxic" why don't you explain what exactly that means? How much more neuorotoxic is it than Dexedrine. Dexedrine not neurotoxic you say, well what if the person who needs Desoxyn has to take 20 times the dose of Dexedrine that most other people do, just to stay awake. There are no study comparing 20 times the average dose of dexedrine to a normal dose of Desoxyn.
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> > > Your example is a poor, if a person needs only 5mg of Desoxyn to do what 100mg of Dexedrine does, then it's pretty obvious that you would take Desoxyn but it's not likely that Desoxyn is 20 times more potent than Dexedrine.
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> > > I would like Chemist's opinion on the difference between Desoxyn and Methamphetamine.
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> > > Cheers,
> > > Panda.
> > >
> > hi there, chemist here....desoxyn = (S)-methamphetamine, and dexedrine = d-amphetamine. panda is correct in re: potency. there is a body of literature that reports that methamphetamine is about twice as potent as d-amphetamine. potency is derived from dose/response evaluations of subjects, and i can point you to several citations that conclude that (S)-methamphetamine and d-amphetamine are actually equipotent. HOWEVER, it turns out that (in at least 1 study examining a D_{1} antagonist) the mechanisms of neurotoxicity at high doses of desoxyn and dexedrine are different, as the antagonist protected against death from dexedrine in a dose-dependent fashion but not for desoxyn. (Derlet et al., Life Sci. 47:821-827 (2000)). but, the equipotency has been established, too. [e.g., Woolverton et al., Pharmacol. Biochem. Behav. 13:869-876 (1980)]. but then, see Peachey et al., Psychopharmacology 51:137-140 (1977) for evidence of greater stimulation (not potency) of desoxyn than dexedrine. more recently, Melega et al. JPET 274:90-96 (1995) concluded that low doses of either drug exhibited similar pharmacokinetics and dopamine response, although this is not a measure of potency nor were the doses extreme. from an abstract by Ellison and Switzer in Neuroreport. 25:17-20 (1993), they report (i quote) ``Both [dexedrine] and [cocaine] induced pronounced degeneeration in fasciculus retroflexus, but only [dexedrine] further induced substantial degeneration in striatum...[Desoxyn] administered in the very high dose but less prolonged drug regimen often employed in studies of dopamine toxicity induce pronounced degeneration in striatum, but widespread degeneration in many other regions as well.'' and then there is one paper by the man who instigated the FDA to make MDMA illegal: Ricaurte et al., Neuropharmacology 22:1165-1169 (1983), in which ``Repeated administration of large doses of [desoxyn] produce long-lasting depletion of brain dopamine and serotonin, as well as persistent decreases in the activity of their respective biosynthetic enzymes...'' interestingly, dexedrine - in ``a comparable regimen'' to the desoxyn dosing - ``did not did not produce long-lasting depletion of 5-HT in either the neostriatum or hippocampus.'' but, it turns out (and not just in this ref) that pretreatment with fluoxetine likely inhibits metabolism of amphetamines in general. so, in summary: potency is derived from dose/response curves, and in low doses, it appears as if desoxyn and dexedrine exhibit similar pharmacokinetics and are somewhat equipotent. however, at high doses of both drugs, the potency of desoxyn is greater and the toxicity is, as well, due to the larger amount of the brain affected in re: dopamine and 5-HT response. most drugs exhibit linear pharacokinetics/dynamics in the recommended dose ranges. the LD_{50} for desoxyn and dexedrine are almost identical, but at higher doses, desoxyn is more lethal. finally, as i posted some time ago, the study by (again) Ricaurte et al. in Science 297:2260-2263 (2003) entitled ``Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA (``ecstact'')'' - which was later retracted because the drugs given to the 5 monkeys tunred out to be methamphetamine and not MDMA - is actually testament to the neurotoxicity to methamphetamine (desoxyn). the dose was 6 mg/kg over 6 hours. recalling that this was pure methamphetamine, this means that your 100 mg desoxyn would correspond to your weight at about 16 kg, or about 35 lbs. 1 monkey died, 1 was unable to continue after the second dose (dosing was 2 mg/kg tid), and the 3 surviving monkeys were examined over several weeks after the acute dosing (there's more, and i can send you the PDF of the article if you desire, or anyone else). conclusions: severe dopaminergic injury and serotonergic neuortoxicity (for subjects using methamphetamine in repeated doses over several hours). the implication is that using desoxyn for a prolonged period - which is essentially what this last study showed - is bad news compared to dexedrine. hope this helps, and all the best, chemist
>hello there, my answers delineated with ***** below.....all the best, chemist
> Hi Chemist great info, I have a few questions thought
> 1 so these were 16kg monkeys given 6mgs/kg of desoxyn over 6 hours, then 2mgs/kg for 2 more dosed six hrs apart?
*** the dosing regimen was 2 mg/kg tid for a total of 6 mg/kg. the reference to the ``second dosing'' is misleading on my part: one of the subjects was going downhill after the second dose, i.e., after ingestion of 4 mg/kg ****> 2 This would correspond to a dose of 420mgs of desoxyn for a 70kg man-no1 not even the worlds worst Narcoleptic would take this, with corresponding follow up doses of 140mgs 6 hrs later, to induce the same dopamine / serotonin damage in the striatum-this being the acute -equiqalent, monkey doses
**** again, 6 mg/kg tid, no additional 4 mg/kg, so your 420 mg dose for a 70 kg man is the right figure, and yes, taken over a 6-hour period. ***
> 3 is this permanent to these neurons or do they grow back-repair
*** according to the literature, the damage is permanent ****
> 4 how would this correspond to my Narcoleptic frend who takes 20mgs 4x daily=80mgs and claims no brain damage after working up to this amount after 45 years, althought he claims to sleep alot when unmedicated, but reports no depression
*** i do not know. perhaps tolerence or something specific in re: mechanism with narcolepsy. the high doses do not result in brain damage, if i understand the phrase to mean reduced mental capability (correct me if i am wrong, please): i did not state that. they result in degradation of dopaminergic and serotinergic receptors. ****
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> 5 How does neurotoxity correspond to Ritalin, for say 40-60mgs for 65kg man, I sometimes think the Rit makes me more tired and other times, to be stimulant-like. feedback?**** don't know, although i assume it is less than methamphetamine. sorry, but that's all i have on ritalin *******
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> Thanks
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poster:chemist
thread:359192
URL: http://www.dr-bob.org/babble/20040627/msgs/362134.html