Phenmetrazine is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron leading to an increase in the release of these monoamines into the extraneuronal space.
Does that make sense? I mean when transporters are blocked less monoamines end up inside the cells. How exactly does that cause
more to be released, when there's a lack of monoamine inside the cell to begin with? Doesn't eqilibrium play some role here? It has been my understanding that the postsynaptic neurons are desensitized due to the excess monoamine (How? Downregulation? Phsphorylation? I have no idea). Well, I mean it would obviously make sense that the cell starts
producing more of the respective monoamine because it is tricked into thinking there is too little of it, but that would take a few days, right? It sure shouldn't cause a "rush" as one or two people have claimed can be experienced when smoking or injecting the substance intravenously.
I really know next to nothing about reuptake inhibitors, but that quote sounds very confusing. If the authors were as confused as I am now, it's probably not a very reliable source...

However, like I said before, structural modifications can indeed cause a releaser to become a reuptake inhibitor. The Fluor group shouldn't have that big an effect though, should it??
I could even imagine it doing both btw. Just look at how complex the pharmacodynamics of amphetamine are and it becomes apparent that it is not always as simple as classifying drugs into two categories.
The dopaminergic part of amphetamine effects as far as I understand them:
- Competitive inhibition of dopamine transporters since amphetamine docks to it the same way dopamine does
- Binding to TAAr-1 (trace amine associated receptor) ---> Here it activates enzymes which phosphorylate DAT's (the dopamine transporter that sits inside the cell membrane)
----> phosphorylated DAT's are internalized, can't transport dopamine anymore
- Binding of amphetamine to VMAT2 (vesicular monoamine transporter) in which it replaces dopamine and therefore causes it's release from VMAT2 vesicles
----> The dopamine is then released and so is the amphetamine
Anyway, you can see both reuptake inhibition as well as release play a large role in what effects amphetamine elicits. It is a very simplified version and doesnt take into account the noradrenergic neurons and the interactions between the two systems.