Comment · Thu, December 1, 2016 · Ceretropic & Nootropics Depot
What causes DXM's afterglow effect?
Original post in this thread
baccheion · 6 points
Serotonin? Opioid receptors interactions? Upregulation after NMDA antagonism? Something else?
Maybe there'll be some combination of supplements I can take to mimic/recreate this effect.
What they were answering
hootnoot · 1 points
Is it really though? Sigma1 agonism ime hasn't been all that effective.
How would you describe it? Have you had the chance to try any pure Sig1 Ligands and not 'dirty' compounds? I suppose the only medication that lets you assess the effect somewhat noticably is Fluvoxamine before the SSRI effects overpower.
Furthermore, get enough Deprenyl to the CNS and there's dual Sigma1 agonism(400nM) and MAO-B inhibition. Still...void of AD effect till MAO-A begins to be inhibited. I think Sigma1 is overblown. DXM is most likely AMPA modulation; https://www.ncbi.nlm.nih.gov/pubmed/25804358
u/MisterYouAreSoDumb · Ceretropic & Nootropics Depot
I think they do play a role. It might not be the only role, or even the main role. However, they certainly are a factor.
Reinforcing Effects of σ-Receptor Agonists in Rats Trained to Self-Administer Cocaine
Also, some nootropic effects from sigma-1 agonists: Beneficial effect of the σ1 receptor agonist PRE-084 against the spatial learning deficits in aged rats
No doubt serotonin and AMPA play a role in this with DXM, too. However, I do believe sigma-1 is involved.
It has also been shown that the sigma-1 receptor modulates NMDA-induced dopamine release: [Regulation of NMDA-induced \[3H\] dopamine release from rat hippocampal slices through sigma-1 binding sites](http://www.sciencedirect.com/science/article/pii/S0197018605800051)
NMDA and AMPA receptors are closely linked together.
Also, we have seen that sigma-1 antagonists can mitigate cocaine addiction: Sigma1 \(σ1\) receptor antagonists represent a new strategy against cocaine addiction and toxicity
DXM hits multiple systems, so I am sure the afterglow is a multi-fold effect. I do not think that a selective sigma-1 agonist would give the same afterglow, though.