MIGHT HAVE FOUND THE MoA OF PRL-8-53!(Remember that I'm a layman, this might be completely wrong, but sounds good imo)
Yesterday I realised something, in the background part mentions two studies looking at the cholinergic system. (
http://i.imgur.com/9SfnWy9.png) Dr Hansl mentions that rats might need more cholinergic activity for optimal performance whilst humans might need less (it may be needed to be coupled with less serotoniergic activity and more dopaminergic activity). So I first started looking for Boshes, 1970, nowhere to be found. So I decided to go with Rech, 1968, and found it (
https://cdn.anonfile...73173642411.pdf (feel free to help me understand it more, from what I understand, more acetylcholine = good for rats, but it got to be on the Muscarinic acetylcholine receptors (M1-M5, I'm guessing M1 mainly due to it's placement, maybe M4 too, but it seems weird because it increases cAMP in the cell))).
From what I've read, the cholinergic system plays a great role in cognition, an antagonist would not be good for it. I (well, RawProduce helped me with this, thanks) however didn't know that there were atleast 2 different groups of acetylcholine receptors, muscarinic and nicotinic (I knew that one). From doing some quick research, I've been lead to believe that PRL-8-53 is thus a M1 (Muscarinic acetylcholine receptor M1) antagonist ("worst case" is that it's not selective). The current M1 antagnonists are used for Parkinson's Disease (some (Trihexyphenidyl) of which seem to be dopamin agonists at the same time, which PRL-8-53 also seems to be (Trihexyphenidyl also seems to be resarched for Hunington's Disease, dystonia, and some others)). This would also explain why they tested for motor control (which is failed, or gave a rather small increase).
The dopaminergic increase is not know which receptor is targeted, I'm guessing all of them. The study Dr Hansl cited (
http://www.ncbi.nlm..../pubmed/4936414) says that they used L-Dopa, thus all receptors would be affected. Same goes with the serotonergic activity, MoA unknown. The study used a selective and irreversible inhibitor (Tryptophan hydroxylase), I have not yet seen the study though. Can get it if you want. I do however not believe that PRL-8-53 is an irreversible, selective inhibitor, but that is just random thoughts. The most likely explanation is that it's due to the AcH effect the serotonergic activity goes down, maybe the same with increased dopaminergic activity.
My thoughts about Coluracetam + PRL-8-53 has now changed, I think it might be ok to take them without a risk. If coluracetams MoA is through high-affinity choline uptake, it would not interfere with PRL-8-53, it would most just likely enhance the nicotinic system (idk how it would affect the muscarinic system though. I would however take the PRL-8-53 first.
Another thought is that they might work against each other if the it's the other way around with the MoA of serotonin and dopamine, that it's because of the the AcH is regulated, but I doubt it. (But still, be careful, always start low)
I would really liked feedback if possible. And credit to RawProduce for helping me.
Edited by Nattzor, 07 July 2013 - 04:35 PM.