13 replies to this topic

[medievil]

I"m not really aware of the interaction between both of these receptors as i'm planning to go on memantine as soon as possible i was wondering wheter i may add an ampakine in the future?

[medicineman]

I"m not really aware of the interaction between both of these receptors as i'm planning to go on memantine as soon as possible i was wondering wheter i may add an ampakine in the future?

I don't mean to sound off, but it seems like this question comes up over and over, for the sole purpose of people trying to squeeze a positive answer, amidst all the criticism of mixing an NMDA antagonist with an NMDA primer, ampakines being a group.. AMPAkines prime AMPA receptors, and NMDA receptors need AMPA activity to become active...... by blocking the NMDA receptor with something like l-huperzine or memantine, which bind more strongly to NMDA than magnesium, you will prevent NMDA receptor activation..... Blocking NMDA is ok if there is a pathological issue, but otherwise, I see it as a hindrance to long term potentiation..

plus, if you are healthy, memantine is a nicotinic receptor blocker..... Can anyone explain why you want to block nicotine receptors in a healthy state?

[medievil]

I"m not really aware of the interaction between both of these receptors as i'm planning to go on memantine as soon as possible i was wondering wheter i may add an ampakine in the future?

I don't mean to sound off, but it seems like this question comes up over and over, for the sole purpose of people trying to squeeze a positive answer, amidst all the criticism of mixing an NMDA antagonist with an NMDA primer, ampakines being a group.. AMPAkines prime AMPA receptors, and NMDA receptors need AMPA activity to become active...... by blocking the NMDA receptor with something like l-huperzine or memantine, which bind more strongly to NMDA than magnesium, you will prevent NMDA receptor activation..... Blocking NMDA is ok if there is a pathological issue, but otherwise, I see it as a hindrance to long term potentiation..

plus, if you are healthy, memantine is a nicotinic receptor blocker..... Can anyone explain why you want to block nicotine receptors in a healthy state?

I'm interested in memantine for its tolerance reducing properties, nicotinic antagonism is also neuroprotective against amphetamine neurotoxiticy.

Thx for your answer.

[medicineman]

np. i hope ur also aware that nicotine receptors are vital for memory formation.. if ur young and in college or doing an academic course, blocking Nicotine receptors may not be the way to go.

[medievil]

np. i hope ur also aware that nicotine receptors are vital for memory formation.. if ur young and in college or doing an academic course, blocking Nicotine receptors may not be the way to go.

But apperantly memantine has been shown to improve cognition and tolerance has been reported to occur to the memory decreasing effects. So i dont think it would be all too much of a problem.

[BieraK]

Here is a Russian Study (the leaders of nootropics, the land of noopept, semax and peptides) about simultaneous NMDA receptor blocking and AMPA receptor activation.
http://www.ncbi.nlm....pubmed/20821972

 

 

Eksp Klin Farmakol
 2010 Jul;73(7):6-12.
[Simultaneous AMPA receptor potentiation and NMDA receptor blockade as strategy for creating effective stimulants for cognitive functions]..

[Article in Russian]

Bachurin SO, Grigor'ev VV, Beznosko BK, Bolkunov AV, Kovalev GI, Proshin AN.

Abstract  

New compounds representing derivatives of acyclic isothioureas have been synthesized, which are capable of simultaneously activating AMPA receptors and blocking NMDA receptors. In order to produce cognitive-stimulating effect, of principal importance is the pathway of NMDA receptor blockade produced by the drug. Positive influence is due to the blockade of NMDA receptors either by mechanism of rapid dissociation of intrachannel site or by inhibition of NR2B subunit of NMDA receptor. Substances that only potentiate AMPA receptor currents or only block NMDA receptors have less pronounced effect on memory than substances with ability to simultaneously potentiate AMPA receptor currents and block NMDA receptor currents. Based on these results, it is concluded that the simultaneous potentiation of AMPA receptors and blockade of NMDA receptors may be a new approach to the stimulation of cognitive functions.

 

Of the substances wich I know, apparently the better option is a ampakine without NMDA interaction and a NMDA antagonist like memantine, the best ampakine choice for doing that is IDRA-21... the problem is that I could not access the complete studies about IDRA-21. Sunifiram is not useful for this activates NMDA.

Edited by BieraK, 05 March 2015 - 02:49 AM.

[Metagene]

Here is a Russian Study (the leaders of nootropics, the land of noopept, semax and peptides) about simultaneous NMDA receptor blocking and AMPA receptor activation.
http://www.ncbi.nlm....pubmed/20821972

Eksp Klin Farmakol
2010 Jul;73(7):6-12.
[Simultaneous AMPA receptor potentiation and NMDA receptor blockade as strategy for creating effective stimulants for cognitive functions]..

[Article in Russian]
Bachurin SO, Grigor'ev VV, Beznosko BK, Bolkunov AV, Kovalev GI, Proshin AN.
Abstract


New compounds representing derivatives of acyclic isothioureas have been synthesized, which are capable of simultaneously activating AMPA receptors and blocking NMDA receptors. In order to produce cognitive-stimulating effect, of principal importance is the pathway of NMDA receptor blockade produced by the drug. Positive influence is due to the blockade of NMDA receptors either by mechanism of rapid dissociation of intrachannel site or by inhibition of NR2B subunit of NMDA receptor. Substances that only potentiate AMPA receptor currents or only block NMDA receptors have less pronounced effect on memory than substances with ability to simultaneously potentiate AMPA receptor currents and block NMDA receptor currents. Based on these results, it is concluded that the simultaneous potentiation of AMPA receptors and blockade of NMDA receptors may be a new approach to the stimulation of cognitive functions.

Of the substances wich I know, apparently the better option is a ampakine without NMDA interaction and a NMDA antagonist like memantine, the best ampakine choice for doing that is IDRA-21... the problem is that I could not access the complete studies about IDRA-21. Sunifiram is not useful for this activates NMDA.

Thanks I needed a home for this one.

Anemoside A3 Enhances Cognition through the Regulation of Synaptic Function and Neuroprotection.


Compounds that have the ability to both strengthen synaptic function and facilitate neuroprotection are valuable cognitive enhancers that may improve health and quality of life, as well as retard age-related cognitive deterioration. Medicinal plants are an abundant source of potential cognitive enhancers. Here we report that anemoside A3 (AA3) isolated from Pulsatilla chinensis modulates synaptic connectivity in circuits central to memory enhancement. AA3 specifically modulates the function of AMPA-type glutamate receptors (AMPARs) by increasing serine phosphorylation within the GluA1 subunit, which is a modification required for the trafficking of GluA1-containing AMPARs to synapses. Furthermore, AA3 administration activates several synaptic signaling molecules and increases protein expressions of the neurotrophin brain-derived neurotrophic factor and monoamine neurotransmitters in the mouse hippocampus. In addition to acting through AMPARs, AA3 also acts as a non-competitive NMDA receptor (NMDAR) modulator with a neuroprotective capacity against ischemic brain injury and overexcitation in rats. These findings collectively suggest that AA3 possesses a unique ability to modulate the functions of both AMPARs and NMDARs. Concordantly, behavioral studies indicate that AA3 not only facilitates hippocampal long-term potentiation but also enhances spatial reference memory formation in mice. These multifaceted roles suggest that AA3 is an attractive candidate for further development as a cognitive enhancer capable of alleviating memory dysfunctions associated with aging and neurodegenerative diseases.

http://www.ncbi.nlm....ubmed/25649278/
http://iplab.ust.hk/... Neuropharm.pdf

[BieraK]

 

Here is a Russian Study (the leaders of nootropics, the land of noopept, semax and peptides) about simultaneous NMDA receptor blocking and AMPA receptor activation.
http://www.ncbi.nlm....pubmed/20821972
 

Eksp Klin Farmakol
2010 Jul;73(7):6-12.
[Simultaneous AMPA receptor potentiation and NMDA receptor blockade as strategy for creating effective stimulants for cognitive functions]..

[Article in Russian]
Bachurin SO, Grigor'ev VV, Beznosko BK, Bolkunov AV, Kovalev GI, Proshin AN.
Abstract


New compounds representing derivatives of acyclic isothioureas have been synthesized, which are capable of simultaneously activating AMPA receptors and blocking NMDA receptors. In order to produce cognitive-stimulating effect, of principal importance is the pathway of NMDA receptor blockade produced by the drug. Positive influence is due to the blockade of NMDA receptors either by mechanism of rapid dissociation of intrachannel site or by inhibition of NR2B subunit of NMDA receptor. Substances that only potentiate AMPA receptor currents or only block NMDA receptors have less pronounced effect on memory than substances with ability to simultaneously potentiate AMPA receptor currents and block NMDA receptor currents. Based on these results, it is concluded that the simultaneous potentiation of AMPA receptors and blockade of NMDA receptors may be a new approach to the stimulation of cognitive functions.

Of the substances wich I know, apparently the better option is a ampakine without NMDA interaction and a NMDA antagonist like memantine, the best ampakine choice for doing that is IDRA-21... the problem is that I could not access the complete studies about IDRA-21. Sunifiram is not useful for this activates NMDA.

Thanks I needed a home for this one.

Anemoside A3 Enhances Cognition through the Regulation of Synaptic Function and Neuroprotection.


Compounds that have the ability to both strengthen synaptic function and facilitate neuroprotection are valuable cognitive enhancers that may improve health and quality of life, as well as retard age-related cognitive deterioration. Medicinal plants are an abundant source of potential cognitive enhancers. Here we report that anemoside A3 (AA3) isolated from Pulsatilla chinensis modulates synaptic connectivity in circuits central to memory enhancement. AA3 specifically modulates the function of AMPA-type glutamate receptors (AMPARs) by increasing serine phosphorylation within the GluA1 subunit, which is a modification required for the trafficking of GluA1-containing AMPARs to synapses. Furthermore, AA3 administration activates several synaptic signaling molecules and increases protein expressions of the neurotrophin brain-derived neurotrophic factor and monoamine neurotransmitters in the mouse hippocampus. In addition to acting through AMPARs, AA3 also acts as a non-competitive NMDA receptor (NMDAR) modulator with a neuroprotective capacity against ischemic brain injury and overexcitation in rats. These findings collectively suggest that AA3 possesses a unique ability to modulate the functions of both AMPARs and NMDARs. Concordantly, behavioral studies indicate that AA3 not only facilitates hippocampal long-term potentiation but also enhances spatial reference memory formation in mice. These multifaceted roles suggest that AA3 is an attractive candidate for further development as a cognitive enhancer capable of alleviating memory dysfunctions associated with aging and neurodegenerative diseases.

http://www.ncbi.nlm....ubmed/25649278/
http://iplab.ust.hk/... Neuropharm.pdf

 

:O interesting compound...
-BDNF Properties
-Neuroprotectant
-LTP enhancer
-AMPAr modulator
-non competitve NMDA receptor modulator.
-Memory enhancer.

I am interested in exploring this area... this a recent paper from this year. 
AA3:
here is a source for pulsatilla in the US:
http://www.ebay.com/...=item3f41358817


I have some IDRA-21 but I not have memantine, I will try to buy it.

 

[normalizing]

any updates

[BobbyDick]

Almost every adaptogen is NMDA antagonist and no one is LTP inhibitor. Mild NMDA antagonism is always good.

[normalizing]

useless reply....

[medievil]

Ive read ppl here combine ampakines with memantine with good results, havent ready any anecdotes tough as ive been away from the forum because of a alot of issues.

 

Either way the brain is a cocktail of substances that do the complete opposite and they work togheter, so its only logical wed also see symergism here.

[normalizing]

what happened buddy, what issues? anything related to stuff you have been taking? you are quite the experimental rat

[medievil]

what happened buddy, what issues? anything related to stuff you have been taking? you are quite the experimental rat

I used to be really much more dilusional, like i tought i could get all meds prescribed for ppl here and sell them to them, but that went wrong, ppl paid my money but i cant get my dex script here in the uk, and my anhedonia is absolutely brain torture (there are differened types of anhedonia for example olanzapine makes me enjoy top gear and see some entertaining effect watching sports, having that can be called anhedonia too) either way i do everything do not go trough anhedonia again wich led me use ppl money and some members here are angry at e for good reason.

 

That said its been going on forever, i cant get stims prescribed, have to order research chemicals leaving me without money.

 

I can safely say that if ppl with this kind of severe anhedonia would kill themselves if they wouldnt see a day out, what i do is try to stay asleep non stop and hope for the love of god the days pass so i can get more stims, i dont have enough money to cover me all the time, only 50% of the time.

 

Living life is impossible for me, i start doing stuff and then i collapse in anhedonia, its fucking bullshit.

 

I abstained from the forum for a bit as a pretty much ripped some ppl off without intending too, basicly impaired shizo thinking because a few times i could randomly get stuff under diff names and they caught up with me, and then facing anhedonia i used the money. I keep saying i want to pay ppl back but i think i can only do it if i have a dex script, which i should be able to get in belguim.

 

As an aside another interesting recovery from shizo, i can remember again, like things that happened in the past, childhood, you see the memory in your brain and feel the emotion, one of the many things that shizo stole of me, it removes everything that makes you human.

 

Either way i dramatically improved in some ways, worse in other ways and the experimenting continiues!