One of the hardest and most festering dilemma's is potentiating/increasing NMDAR function/integrity , so in order to (or in hopes of) increasing LTP (Long-Term-Potentiation) and Synaptic Plasticity. The NMDA (N-Methyl-D-Aspartate) Receptor is an Ionic Glutamate Receptor (1) which can be activated by several ligands/amino acids..such as Aspartic Acid, Glutamic Acid, Glycine and D-Serine (2) (3).
However, it's function is dependent on how much of a 'block' or interference there is from other molecule's; notably the Zinc (Zn2+) and Magnesium (Mg2+) ions (4) (5). Magnesium blockade of the NMDA receptor complex can be easily removed without stopping the majority of Magnesium's benefits by using the memory enhancing drug NEFIRACETAM (6).
Until now , however, there has been no clear way to actually reduce or eliminate the Zinc (Zn2+) inhibition of the NMDAR. Tyrosine Kinase Src is a non-receptor protein complex that , when activated, directly reduces/decreases Zinc ion inhibition of the NMDA pathway; effectively restoring memory functions and proper expression of the NMDA receptor/s (7).
Activating the protein isn't exactly simple - as there isn't a specific drug to directly activate it. However, there are other various supplements and endogenous modulators that can be manipulated to do so.
The first method, which is not sex-specific, would be a combination of Pregnenolone and DHEA Sulphate. These two hormones are easily available over the counter or over the Internet and they act in similar ways.
Pregnenolone acts as a positive allosteric modulator of the NMDA-receptor; and effectively displaces antagonists from binding with it - thus removing some inhibitory influences (8) (9).
DHEA/DHEA-S on the other hand, directly stimulates tyrosine kinase/Src to reduce the Zinc block on the NMDA Receptor (10) (11) (12).
Finally, increasing Testosterone, or more specifically, the male-hormone 5-alpha-dihydrotestosterone (DHT) - directly increases Src gene activity and directly amplifies/increases NMDA receptor activity; especially in the Hippocampus where it is needed most (13) (14).
My recommended {SAFE} methods of completing this Task are to use a Proven DHEA/Pregnenolone combination in a transdermal solution (Cream/Gel). Oral DHEA/Pregnenolone shows very LOW bioavailability (!).
- RS Transaderm is the best way to do this.
- Andractim DHT Gel is the fastest way to increase DHT-hormone levels.
For the DHT-part, you could also use Tribulus, but it would be *MUCH* weaker than using the Gel, I don't even know if it would be effective for this task (Probably Not)..
FINAL NOTES : Pregnenolone also blocks GABA-A Receptors in specific portions of the Brain which may be one additional mechanism by which it enhances/allows for the activation/re-activation of NMDA-Receptors and it's descending pathways.
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