4 replies to this topic

[Christian Hunter]

Between the two nicotinic agonists, which do you believe more likely to enhance cognition in otherwise healthy adults?

 

Lastly, do you believe either pose any material side-effect profile or toxicity risk?

 

Any additional thoughts welcome.

 

Christian Hunter

Austin, TX

[megatron]

I'm sure you mean EVP-6124. From the studies I've read, it would seem like GTS-21 has given the most significant improvements among the current modulators of the alpha-7 receptor tested in humans. 

[Christian Hunter]

I agree with you on GTS-21, but to my knowledge it can't yet be procured (w/ exception perhaps to to the group buy I've seen on this site), right?

 

And UGH, you're right, I meant "EVP-6124"; not sure if I can edit my original post but will look to do that now.   Thank you for your prompt reply.

 

My question to you however: do either EVP-6124 or SEN-12333 (WAY 317,538) interest you, and would you take either (or both) if handed the opportunity?

 

Thanks again, 

 

Christian Hunter

Austin, TX

[Flex]

From my amateurish knowledge I would use the partial agonist, so the EVP-6124.

 

The thing is this:

Partial agonists do activate ( in this case) a post-synapse to a certain extend, which can vary from, dont know, 10% to 90%,

depending on the molecule property.

If the activation is too low but the competitiveness is approximately as strong as the neurotransmitters, it would lead to a lesser activation i.e. decrease.

 

In contrast, the own body neurotransmitters do activate it to 100% like a full agonist. Which sounds good, but it is acompanied by a receptor desentisation.

The desensitation leads to a, so to say, callus which needs more and more neurotransmitters to activate the synapse to the same level as before accompanied with a receptor up or down regulation.

So this is one of several mechanisms of the homeostasis.

 

Btw: I heard that somkers do lost nicotinic synapses after a long period so arround 15 years. which differs from the usual receptor up/down regulation and is "afaik" kind of permanent.

 

To prevent a desentitaion and to ensure a longtermed effect, is either a cycling of the Full agonist needed (which is seemingly difficult)

or the usage of a partial agonist which shouldnt activate the synapse too much or too little.

 

Be aware that I could mistakenly told something wrong. So therefore I dont guarantee anything about those infromations.

 

 

 

 

 

Edited by Flex, 25 June 2014 - 09:50 AM.

[medicineman]

Continuous stimulation of Alpha 7 via beta amyloid is thought to be one of the causes of toxicity to the receptors themselves. I'd stick to partial agonists.