I get asked a lot about how CILTEP™ relates to other commonly taken nootropics, such as the racetam family (Piracetam, Phenylpiracetam, etc.). It’s an important question in determining how to optimally enhance cognition. Cognition takes place in multiple sequential steps that execute in parallel in different parts of the neural anatomy in response to electrical and chemical signals. Appropriately optimizing each one of these steps without over stimulating is, in my opinion, the best means to improve cognition. I also find it more effective to seek to optimize cognition in a non-overlapping way in which molecular biological systems are addressed separately by each intervention.
I find the racetam family and CILTEP™ complement each other in this manner with racetam family working to optimize interaction with glutamate and electrical signaling in an interneuronal context at the synaptic cleft while CILTEP™ optimizes operation of secondary messengers inside the neuron on an intraneuronal basis by triggering long term potentiation (LTP) via adenylyl cyclase without activating the D1/D5 receptor which normally uses this pathway to enhance LTP.
LTP begins when an electrical signal known as an action potential reaches the axon terminal of an excitatory synapse. This causes the neurotransmitter glutamate to be released into the synaptic cleft. This activates AMPA and NMDA receptors on the postsynaptic neuron. The incoming action potential causes depolarization via the AMPA receptor which, if strong enough, eventually displaces magnesium ions blocking the NMDA receptor. The NMDA receptor then depolarizes via sodium and calcium ions that enter the cell. These calcium ions cause the phosphorylation of AMPA receptors via CAMKII, increasing their ability to depolarize the cell during subsequent stimulation. The calcium ions also induce the insertion of AMPA receptors into the postsynaptic membrane by triggering other intracellular mechanisms. These two factors cause a strengthening of signal transduction at the synaptic cleft. This is one of the mechanism of early LTP.
Piracetam and other members of the racetam family have been shown in studies to increase the number of NMDA receptors present in the synaptic cleft. They also can act as positive allosteric modulators at the AMPA receptor, meaning they can enhance the function of this receptor though they do not activate it directly as glutamate would. This mechanism of action has the effect of more easily strengthening electrical signaling between neurons and thus theoretically increasing the process that can eventually lead to LTP or another form of synaptic plasticity known as Long Term Depression (LTD).
The late phase of LTP, in which potentiation in response to action potentials are more permanently strengthened occurs when calcium influx increases levels of Ras-GTP which begins a complex kinase cascade which eventually results in the activation of the transcription factors Elk-1 and CREB. These transcription factors trigger the creation of new proteins in the nucleus and mitochondria.
Another process by which CREB can be activated is by adenylyl cyclase activity which increases cAMP. This process can be triggered endogenously when the g-protein coupled D1 receptor is activated in response to dopamine. cAMP generated by adenylyl cyclase interaction with ATP in the neuron is regularly degraded by PDE4. This degradation of cAMP decreases cAMP’s activation of CREB. Forskolin is well known to increase intracellular levels of cAMP via adenylyl cyclase. Various herbal and synthetic PDE4 inhibitors such as Luteolin in artichoke extract can inhibit the activity of PDE4 and thus prolong cAMP’s activation of CREB. The end result is that LTP is promoted, but via a different pathway than the racetam family.
Thus theoretically the early phase of LTP is enhanced by the racetam family which can also triggers late LTP via Ras-GTP. This activity is possibly further enhanced by the cAMP increasing activity of forskolin and PDE4 inhibiting activity of luteolin in artichoke extract which could theoretically trigger LTP via cAMP’s activation of CREB.
In summary, we can determine that, at least in theory, there is evidence that the racetams and CILTEP™ should synergistically interact such that they would both optimize and enhance the late phase of LTP while the racetams can improve the early phases of LTP and LTD as well.
Get CILTEP™ Formulated by its creator Abelard Lindsay exclusively for Natural Stacks, CILTEP™ is natural way to stay focused, alert, and motivated for hours. Dave Asprey, The Bulletproof Executive has said, “CILTEP has earned a place alongside world-class smart drugs like piracetam, gingko, and choline. It works synergistically with them to help you do – and be – more.” Purchase today and save $10 with coupon code racetams.
Formulated by its creator Abelard Lindsay exclusively for Natural Stacks, CILTEP™ is natural way to stay focused, alert, and motivated for hours.
Dave Asprey, The Bulletproof Executive has said, “CILTEP has earned a place alongside world-class smart drugs like piracetam, gingko, and choline. It works synergistically with them to help you do – and be – more.”
Purchase today and save $10 with coupon code racetams.