Comment · Fri, June 2, 2017 · Ceretropic & Nootropics Depot
Who can we get to synthesize this?
What they were answering
CL20 · 2 points
Also, traditional benzodiazepines fully maximizes (hyperpolarizes) the chloride ion channel, which makes another firing less likely, and repeated usage dampens the synaptic ending in the long term (down regulation), this substance never "fully" maximize the chloride ion channels, which is why, the author states, is is not addictive.
10+years of daily, heavy, Kava users, do not meet DSM-IV, yet 10 days of a traditional benzo does. It seems that, this mechanism of "never maximizing GABA chloride ion channel", polarizing GABA chloride channels to a certain degree, without ever hyperpolarizing it, sounds like the key of not inducing tolerance to GABA-PAMs, thoughts ?
/u/MisterYouAreSoDumb
u/MisterYouAreSoDumb · Ceretropic & Nootropics Depot
I think that's accurate. Also, the GABA and nACh systems are closely linked, and agonism/antagonism affects the expression/activation of the other. We know the α4β2 nACHRs are crucial in the formation of addiction, and that activation of the nACh receptors affects GABA expression. It's not unreasonable to assume that the mechanism can work the other way around, with hyperpolarization of the GABA receptors causing up-regulation of the α4β2 nAChRs, or even the α3β4 nAChRs. Partial agonism of the GABA receptors, or positive allosteric modulation, might not affect the expression of those nicotinic ACh receptors that lead to addiction.