Racetams/Ampakines + Dopaminergic Stimulants = Pharmacological Interaction ?

[Ektor]

What would be the effect on the brain, neurons and neurotransmitters of the combination of Piracetam-like drugs and Amphetamine/Cocaine type of stimulants?
Would it increase neurotoxicity?

Stimulants (as far as i know)work to increase the concentration in the synaptic cleft of Dopamine, Noradrenaline and Serotonin either by reuptake inhibition or direct release. How would this effect relate to global brain function and other neurotransmitter systems?
Dopaminergic stimulants are also able to cause an indirect release of B-endorphin or other opioid peptides in the parts of the brain regulating pleasure giving a feel good state. What do this kind of stims do to glutamate levels and general glutamatergic neurotransmission?

Piracetam and ampakines are positive allosteric modulators of glutamate AMPA receptor, this indirectly facilitates the opening of the NMDA receptor's ion channel so piracetam/ampakines positively modulate AMPA and NMDA glutamate receptors, both of these involved in long term potentiation, which is a mechanism to encode new memories.
Piracetam also elevates/facilitates neuronal mitochondrial metabolism, giving the heightened mental energy that many piracetam users feel.
In addition to all this, piracetam lowers hippocampal acetylcholine levels but upregulates (maybe all brain's) acetylcholine nuscarinic M1 receptors, also the cholinergic system is involved in memory/cognition but i dunno the actual meaning of this dual action.
How piracetam's effects relate to the monoaminergic systems?


Stimulants increase synaptic levels of catecholamines, which are mostly Excitatory Neuromodulators, Piracetam on the other hand increases the efficiency of glutamate which is the main Excitatory Neurotransmitter, will there be a synegistic effect?
Stimulants also elevate serotonin levels and piracetam has cholinergic effects, how do this two additional systems play their role in combination of all the above??

Lets begin an interesting conversation!!!!

 

[Epsilon Alpha]

What would be the effect on the brain, neurons and neurotransmitters of the combination of Piracetam-like drugs and Amphetamine/Cocaine type of stimulants?
Would it increase neurotoxicity?

Probably, you're pretty much prying open AMPA and NMDA receptors. Even if piracetam doesn't elevate intracellular Ca2++ levels it would still likely up your tolerance in record time given our understanding of NMDA's role in amphetamine induced behavioral changes.

Stimulants (as far as i know)work to increase the concentration in the synaptic cleft of Dopamine, Noradrenaline and Serotonin either by reuptake inhibition or direct release. How would this effect relate to global brain function and other neurotransmitter systems?
Dopaminergic stimulants are also able to cause an indirect release of B-endorphin or other opioid peptides in the parts of the brain regulating pleasure giving a feel good state. What do this kind of stims do to glutamate levels and general glutamatergic neurotransmission?

Piracetam and ampakines are positive allosteric modulators of glutamate AMPA receptor, this indirectly facilitates the opening of the NMDA receptor's ion channel so piracetam/ampakines positively modulate AMPA and NMDA glutamate receptors, both of these involved in long term potentiation, which is a mechanism to encode new memories.
Piracetam also elevates/facilitates neuronal mitochondrial metabolism, giving the heightened mental energy that many piracetam users feel.
In addition to all this, piracetam lowers hippocampal acetylcholine levels but upregulates (maybe all brain's) acetylcholine nuscarinic M1 receptors, also the cholinergic system is involved in memory/cognition but i dunno the actual meaning of this dual action.
How piracetam's effects relate to the monoaminergic systems?

Stimulants increase synaptic levels of catecholamines, which are mostly Excitatory Neuromodulators, Piracetam on the other hand increases the efficiency of glutamate which is the main Excitatory Neurotransmitter, will there be a synegistic effect?
Stimulants also elevate serotonin levels and piracetam has cholinergic effects, how do this two additional systems play their role in combination of all the above??

The only existing literature I've found shows this is the case in rodents. http://www.ncbi.nlm.nih.gov/pubmed/22607774

Piracetam has a bizarre effect on various ion channels (particularly cation channels) so its effects on a single neurotransmitter basis are hard to gauge.

Lets begin an interesting conversation!!!!

Holy fuck there are a lot of recent papers on racetams. Assuming piracetam has the same kind of effects on inflammation as noopept it might have some sort of neuroprotective effects if it doesn't cause a intracellular maelstrom of intracellular free calcium.

 

[Ektor]

i know there are lots of papers on racetams, as there are on stimulants, but papers on their combination are pretty rare. There is a couple of studies on rat and most of the material is just behavioral studies, they basically say that piracetam when combined with amphetamine increases motor activity more than amph alone. What would be interesting to know is:
-Does piracetam coadministration alter dopamine and other monoamines level in respect to stimulants alone?
-How do stimulants affect Long Term Potentiation and NMDA/AMPA transmission when combined with piracetam?
-Does piracetam have an effect on stimulants' indirect endorphin release/endogenous opioid activity?

 

[AlphaMethylPhenyl]

im interested too

 

[N0 W4RN1NG]

Subscribed. I take amphetamine daily, and sometimes (rarely) add a dose of noopept in for enhanced memory. Cramming for exams, etc.

I feel a synergy, although it isn't really an enhancement of euphoria, but rather functional work capacity.

I am very curious about what that is doing to my brain - as another poster mentioned, I worry excessively about rapid tachyphylaxis, and this is why I don't allow myself to use the noopept + amp combination more frequently.

Another avenue I have considered, but not pursued, could be the addition of a NMDA antagonist. The NMDA ant. + AMP combo is nothing new - but how would adding noopept or another racetam influence this? Surely it seems vulgar, to antagonize and upregulate a receptor simultaneously, and usually the effects of such interactions are not easily predictable. But in theory, what could the possible consequences be? The motive, of course, would be to keep the AMPA upregulation of noopept, but bar NMDA upregulation, facilitating enhanced cognitive abilities without the propensity to develop a worse tolerance to amphetamines.

 

[Ektor]

That what sounds good, keep the AMPA an leave the NMDA, all this while having high dopamine level. It sounds like a good long term full power cognition enhancer combo!!! by the way, favoring AMPA transmission while blocking NMDA is the supposed mechanism for ketamine antidepressant action..
Sounds interesting!!!

I recently tried the piracetam/cocaine combo, and even if coke remains mostly a recreational and not so productive stimulant piracetam made the coke high feeel a lot cleaner and clearer in the head. It was like having more control on the big energy and confidence boost of cocaine, very nice after all..
Anyway cocaine still remains incredibly addictive on my person so probably i should (sadly) refrain to do it anytime soon and beware of its crazy cravings.
On the other end speed/amphetamine is almost non addictive on me and could be a better candidate to explore the nice empowering stimulant/nootropic combination!!!

Boom!!!