Comment · Wed, June 15, 2016 · Ceretropic & Nootropics Depot
Which nootropic can upregulate GABA A receptor?
Original post in this thread
homosuperiorr · 3 points
How to decrease clonazepam tolerance?
Tolerance results in a desensitization of GABA receptors and an increased sensitization of the excitatory neurotransmitter system, glutamate such as NMDA glutamate receptors.
Other changes that occur are the reduction of the number of GABA receptors (downregulation).
https://en.wikipedia.org/wiki/Benzodiazepine_dependence#Mechanism
So GABA A antagonist and/or GABA A upregulator and NMDA antagonsit would work, yes?
What they were answering
misterbailey69 · 2 points
I'm not an expert in reading this sort of stuff, so I'm not at all sure about this, but, in the Kava references you gave, I can't find anything that I understand to be saying specifically that Kava upregulates GABA receptors. Can you point it out/explain it to me? Or locate another reference?
I would be very pleased if Kava did do this, since the other alternative---Bacopa---gives me bad side effects (serious emotional blunting).
u/MisterYouAreSoDumb · Ceretropic & Nootropics Depot
Sorry, I only linked the abstract. Here is the full study.
the number of GABA binding sites was significantly enhanced in the presence of both the high and the low concentration of kavapyrones in all brain areas investigated except CER. This region displayed a significant enhancement in Bma x relative to control only at a kavapyrone concentration of 500 taM (P < 0.001).
Consistent with the regionally different activity of the kavapyrone enriched extract to stimulate [3HI muscimol binding, the increases in the maximal number of binding sites (Bronx) induced by our extract showed a marked brain-regional variation. Region-dependent differences in the increase of Bma x occurred in the presence of both the higher 500 pM and the lower 100 pM concentration of kavapyrones. At a concentration of 500 gM H I P and AMY displayed the highest increases (by 370 4- 57% and 328 4- 12%, respectively) which were of similar magnitude and varied significantly fi'om that observed in M E D (increase by 263 + 14%) (P < 0.05). The enhancement in FC (by 166 __ 19%) was significantly lower than that observed in M E D (P < 0.01) and AMY (P < 0.00t) but significantly higher than that found in CER.
The results of the present investigation demonstrate that the kavapyrone enriched extract is capable of potentiating the binding of muscimol to GABAA receptors in membrane fractions of the brain centers that are responsible for mediating the sedative kavapyrone action. This correlates with its pharmacological activity as a central nervous system tranquilizer. The enhancement of muscimol binding is due solely to an increase in the density of binding sites. This mechanism is similar to that of both barbiturates and anaesthetic steroids which also enhance GABA agonist binding by increasing the apparent number of binding sites that involves an increase in the affinity of previously undetectable, very low affinity binding sites (Olsen and Snowman 1982; Yang and Otsen 1987; Peters et al. 1988).
Muscimol is a GABAa receptor agonist, which is why they are referencing it a lot. That study showed that kavapyrone, which is found in kava, increased the number of GABAa binding sites.