Comment · Thu, January 21, 2016 · Ceretropic & Nootropics Depot
Long-lasting downregulation of GABAergic synapses after repeated administration of anxiogenic drugs - possible implication for Fasoracetam?
Original post in this thread
I_Strahd · 5 points
Hello there,
I've been experimenting with a bevy of noots over the past couple years - and over that time, have remained consistently interested in fasoracetam for it's apparent potential in up-regulating the gaba system.
However, the use of gaba antagonists, for which this compound is considered, is still - in general - a mystery to me in terms of their long-term effect on an otherwise healthy brain.
Then today I happened upon this old study, which seems to make the case that:
"a long-lasting down regulation of GABAergic synapses can be obtained after repeated administration of anxiogenic, proconvulsant and convulsant negative modulators of GABAergic transmission. The latter finding further suggests that GABAergic synapses undergo rapid and persistent plastic changes when the GABAergic transmission is persistently inhibited."
http://www.ncbi.nlm.nih.gov/pubmed/1981393
and I'm left wondering...if fasoracetam's primary method of action is to antagonize gaba(b) receptors, will this, in actuality, have a negative impact on the functioning of the gaba system?
Similarly, will this mechanism hold,. in general, for all gaba antagonists?
And lastly, what is to be made of this c…
What they were answering
DeltruS · 1 points
I get phenibut-like effects from lavender too. Of course no motivational / drunk feeling overlap, but similar feeling pain reduction, wakefulness, visual and mental clarity.
I have some sort of nervous system disease like chronic fatigue syndrome / fibromylagia although most people I've talked to with the the same problems don't get the same effect from the drug so who knows. There are tons of unknown subtypes of the syndromes. This is probably why lavender/phenibut feel so nootropic for me but not others, I'm a bit different.
I believe the phenibut-like effects of lavender are from its constituent linalool: http://www.sciencedirect.com/science/article/pii/S1043661800906716
So overall what I'm saying is that while painkilling effects maybe be α2-δ VDCC related, VDCCs can also be involved with processes involving cognition and disease.
Here's an interesting paper on VDCCs:
http://moscow.sci-hub.bz/137cc45835e85ead8abc4ddd1a68b767/10.1016%40s0959-4388%2803%2900066-7.pdf
http://moscow.sci-hub.bz/2ad4b7195b13dbd791dc75b9d7470a67/10.1038%40nature11033.pdf
Also VDCC's are involved in both the action potential and chemical cascade that releases neurotransmitters: https://en.wikipedia.org/wiki/Action_potential#Chemical_synapses
The arrival of the action potential opens voltage-sensitive calcium channels in the presynaptic membrane; the influx of calcium causes vesicle…
u/MisterYouAreSoDumb · Ceretropic & Nootropics Depot
See I also get some similar effects with lavender extract and phenibut. This includes rebound symptoms. I do not get any of the dopaminergic mood-boosting effects with lavender extract, though.
Lavender Oil-Potent Anxiolytic Properties via Modulating Voltage Dependent Calcium Channels
We show for the first time that lavender oil bears some similarities with the established anxiolytic pregabalin. Lavender oil inhibits VOCCs in synaptosomes, primary hippocampal neurons and stably overexpressing cell lines in the same range such as pregabalin. Interestingly, Silexan does not primarily bind to P/Q type calcium channels such as pregabalin and does not interact with the binding site of pregabalin, the α2δ subunit of VOCCs. Lavender oil reduces non-selectively the calcium influx through several different types of VOCCs such as the N-type, P/Q-type and T-type VOCCs. In the hippocampus, one brain region important for anxiety disorders, we show that inhibition by lavender oil is mainly mediated via N-type and P/Q-type VOCCs.
So it does not bind to the same α2δ subunit as Phenibut does. However, it is modulating calcium influx through other VDCCs. Do you get rebound anxiety/depression when coming off lavender extract?