Talk:Monoamine releasing agent

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Mechanism

@Petergstrom: What I deleted in this edit is not "new research" which contrasts with what is written there. It's describing a downstream effect of TAAR1 agonism: the phosphorylation of a monoamine transporter by PKC which induces the directional reversal of monoamine transport through a plasma membrane monoamine transporter (i.e., DAT, NET, or SERT). TAAR1 activates the PKC phosphorylation cascade.

The disruption of the pH gradient that was mentioned is a specific hypothesis about how these drugs induce monoamine release from vesicular stores through VMAT2, but not necessarily inhibit reuptake through VMAT2 (e.g., amphetamine and methamphetamine respectively displace tetrabenazine and reserpine from their respective binding sites on VMAT2 - those drugs are VMAT2 reuptake inhibitors that do not induce efflux through VMAT2). While I believe that the hypothesis is likely correct, I'd wait until it is verified before covering it as an actual mechanism of monoamine release. For now, I think it's sufficient to simply say that these drugs inhibit VMAT2 reuptake and induce monoamine release through VMAT2. Seppi333 (Insert 2¢) 21:53, 6 January 2017 (UTC)[reply]

"noradrenergic drugs (like) ephedrine (...) trend towards liking"

I'm curious as to what in the linked source justifies the claim that selective norepinephrine releasing agents are rewarding and/or recreational by any stretch of the meanings. Ephedrine is not a selective NRA, its selectivity for inducing NE release over DA can be as low as 5,5 to 1, which is nowhere near what's considered selective. A singular pilot study done on non-drug users about an MRA drug not selective for norepinephrine doesn't prove the outlandish claim that "noradrenergic drugs" are rewarding. Suggesting that said "noradrenergic drugs" are rewarding is also contradicting the well-documented aversive CNS effects of selective norepinephrine reuptake inhibitors and direct adrenergic agonists.

My guess is that a misunderstanding that phenylpropanolamines are selective NRAs somehow exists because those drugs are often considered selective sympathomimetics, which has nothing to do with actual selectivity for NE release and everything to do with low blood-brain barrier penetration relative to amphetamine and methamphetamine. Reph-415 (talk) 17:40, 12 August 2023 (UTC)[reply]