Comment · Mon, October 12, 2015
Chiral Pharmacokinetics of MDMA and its Phase I and II Metabolites following Controlled Administration (2015)
What they were answering
MBaggott · 1 points
It actually does not directly measure the neurotoxicity of any of the compounds.
Really?? Now I'm really worrying about your reading comprehension. The paper _does_ measure neurotoxicity, in so far as any measure of SERT is an index of neurotoxicity. It's in Table II, as I stated, the logic of which is described in the methods under a section called "Neurotoxicity Studies" which states “Significant reduction in the Bmax value, which is a measure of the density of 5-HT uptake sites, relative to saline-treated controls was interpreted as evidence of ablation of serotonergic terminals resulting from neurotoxicity."
Would we not then correct it for allometric scaling to humans, to get a more accurate picture?
Allometric scaling is used as a proxy for pharmacokinetics when you don't have pharmacokinetics. Here, we have pharmacokinetics and would be well advised to use actual exposures rather than rules of thumb. More generally, allometric scaling is considered less than useful when there are active metabolites, since smaller animals tend to make more metabolites than humans. (Also, metabolic pathways of amphetamine-like drugs vary between species and have been hypothesized to depend on dietary patterns.)
There's a whole literature discussing why scaling doesn't really work with MDMA such as [my note with Vo…
u/MisterYouAreSoDumb
You are correct to worry about my reading comprehension, because I completely overlooked that section. I apologize.
Do you have a link to the study showing the pharmacokinetics of MDA in rats at the various dosages?