for the neurotoxic MPTP MPP+ type mechanism it needs to be able to form a stable permanently charged species by oxidation.
for this reason 4-benzyl 1 methyl tetrahydropyridine is not neurotoxic.
also anything with no alkyl on the pyridine/pyridine tetrahydropyridine nitrogen are not neurotoxic. as they cannot form a permanently charged species that gets stuck in the neurons.
I am not certain of the mechanism by which MPP+ does the damage, but there does seem to be something involving oxidative stress caused by the massive increase in cytoplasmic dopamine. it also seems to be able to damage the mitochondria in dopamine neurons.
I have heard that the notorious neurotoxin MPTP is a known contaminant in commercial merpedine/pethidine but there are no reports of lasting parkinsons like effects. so perhaps low levels of MPTP doesn't have cumulative effects, it requires a single dose to kick of the damage. messing with 1-alkyl tetrahydropyridines is just a really bad idea, as bad as trying to get loperamide through the blood brain barrier.
2-benzyl piperidine seems pretty safe, though also relatively impotent as a stimulant from what I have heard and read. active at over 100mg. it is a relative of methiphenidate.
2-benzyl piperazine is also a known stimulant, though whether it is worthwhile???
on the whole the N-phenyl piperazines seem to have too much in the way of 5ht2c agonism with not a lot else, leading to panic reactions. pretty useless really, and if they weren't industrial intermediates they would simply not be available, no one would bother custom synthesizing them.
for this reason 4-benzyl 1 methyl tetrahydropyridine is not neurotoxic.
also anything with no alkyl on the pyridine/pyridine tetrahydropyridine nitrogen are not neurotoxic. as they cannot form a permanently charged species that gets stuck in the neurons.
I am not certain of the mechanism by which MPP+ does the damage, but there does seem to be something involving oxidative stress caused by the massive increase in cytoplasmic dopamine. it also seems to be able to damage the mitochondria in dopamine neurons.
I have heard that the notorious neurotoxin MPTP is a known contaminant in commercial merpedine/pethidine but there are no reports of lasting parkinsons like effects. so perhaps low levels of MPTP doesn't have cumulative effects, it requires a single dose to kick of the damage. messing with 1-alkyl tetrahydropyridines is just a really bad idea, as bad as trying to get loperamide through the blood brain barrier.
2-benzyl piperidine seems pretty safe, though also relatively impotent as a stimulant from what I have heard and read. active at over 100mg. it is a relative of methiphenidate.
2-benzyl piperazine is also a known stimulant, though whether it is worthwhile???
on the whole the N-phenyl piperazines seem to have too much in the way of 5ht2c agonism with not a lot else, leading to panic reactions. pretty useless really, and if they weren't industrial intermediates they would simply not be available, no one would bother custom synthesizing them.
), since the electronegative atom is at the meta position as same as TFMPP and mCPP, which I got a bad reaction (seretonergic related) from both two of these.
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