Transmitter enhancing agents

[dopamimetic]

From what I'm noticing on myself, regarding continuous effects reuptake or degrading (e.g. MAOIs) inhibition doesn't work. There is down-regulation occurring and in the end a general blunting of effects, eventually leading to a pseudo-depressed state. So I'm theorizing that rather the opposite - reuptake enhancing agents - could be promising. I know that this mechanism has been attributed to tianeptine but as a secondary / downstream effect and probably it isn't very strong at this.

Think to remember that we have some rare flavonoid which was supposed to do this for dopamine. And there is colouractem which enhances high-affinity acetylcholine uptake as well as riluzole doing the same for glutamate (absolutely have to try the latter, will require some efforts to get a script for it but I -need- to try it...) Riluzole is said to be neuroprotective and stimulating at the same time, and has showed superior efficacy for many mental disorders from depression over OCD to anxiety (re-adjusting the glutamate system..).

On the first sight, one would think that reuptake enhancement would lead to lower activity of the targeted system, but this doesn't appear to be true. Could it actually cause the systems to become more efficient, while avoiding depletion and maybe even inducing receptor up-regulation at the same time? And when reuptake inhibitors do slow down firing rate, might enhancers do the opposite? What do you think about this?

 

[serotonin2A]

I don't think you are going to gind what you are looking for. Tianeptine is probably not a reuptake enhancer -- that is likey a misinterpretation of the data -- the studies need to be repeated with modern tools. There aren't any other established drugs that work by that type of mechanism.

And it doesn't make a lot of sense to think that reuptake enhancement would produce the effect you are looking for. Uptake inhibitors and MAOIs work by increasing transmission, so if they worked (for a period, until tolerance developed) then it makes no sense to think that going the other direction would produce the same effect.. It could be that your brain is just very good at maintaining homeostasis.

 

[dopamimetic]

Maybe reuptake enhancement is the wrong term, but such transmitter activity promoting agents are possible and actually we have at least two that appear to work- BPAP and PPAP.

(-)-1-Phenyl-2-propylaminopentane ((-)-PPAP) is a drug with an unusual effects profile. It can loosely be grouped with the stimulant or antidepressant drug families, but its mechanism of action is quite different.

PPAP is classified as a catecholaminergic and serotonergic activity enhancer. This means that it stimulates the impulse propagation mediated transmitter release of the neurotransmitters dopamine, norepinephrine and serotonin in the brain (although unlike the newer and more potent compound BPAP, it has less impact on serotonin release and affects mainly the catecholamines). Unlike stimulant drugs like amphetamine, which release a flood of monoamine neurotransmitters in an uncontrolled manner, PPAP instead only increases the amount of neurotransmitters that gets released when a neuron is stimulated by receiving an impulse from a neighbouring neuron.

This is distinct from the reuptake enhancers like coluracetam & riluzole, but from the reports saying that riluzole is actually stimulating, and coluracteam has nootropic properties, this way of action seems to be possible too.

 

[Cotcha Yankinov]

I thought I would throw out here the discovery that tianeptine is a full agonist at mu and delta opoid receptors http://www.tianeptine.com/opioid.html

Can you manipulate the SERT levels through antagonizing 5-HT2B?

But I wonder if somebody responds poorly to SSRIs (they get insomnia/mild mania for example) if an uptake enhancer is what they need instead, assuming the original response of insomnia/mild mania to SSRIs isn't transient, transient as in it would go away as 5-HT2A is down regulated etc. but I suppose just as how there are adaptations that are beneficial for some with SSRIs there would likely be the opposite with uptake enhancers.

They might help with mania related things though, seeing as SSRIs cause mania sometimes. Idk how the hell an uptake enhancer works, does it work by some genetic mechanism to signal more reuptake transporters to be generated or something?

 

[aced126]

Couldn't one consider reuptake blockers as kind of "uptake enhancers" as described in this thread. With reuptake blockers, you still actually need an action potential arriving at the synapse for the dopamine to be released, whereas obviously with releasing agents such as amphetamine, you don't need an action potential for the dopamine to be transported out of the neuron.