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Kava Fact of the Day Kava and glycine.

The Kap'n

The Groggy Kaptain (40g)
KavaForums Founder
Kavalactones, glycine, and negative allosteric modulation.


What is glycine?

In the context of today’s fact of the day, glycine is known as an inhibitory neurotransmitter. When glycine attaches to glycine receptors in the nervous system it agonizes the receptor and allows a chloride ion to enter the neuron, reducing its potential for action. This can be seen as a “calming” effect on the nervous system [1].

Strychnine?

You’ve probably heard of this poison, strychnine. Strychnine in the human body is the antithesis of glycine. Strychnine is known as a glycine antagonist. What this means is that when strychnine binds to glycine receptors it prevents the normal inhibitory actions of glycine. So when strychnine binds, it prevents the pore from opening and allowing a chloride ion through. This causes the cell to be hyperpolarized and increases it’s possibility of firing an action. If you get enough strychnine to bind to enough glycine receptors it can cause many rather unpleasant reactions such as generalized muscle spasms and seizures as well as brain damage, kidney failure and ultimately death in high enough doses [2].

How does kava work in regards to glycine?

The constituents of kava were shown to be effective in the reversal of strychnine toxicity in mice [3]. This means there is some competitive inhibition between kavalactones and strychnine. Kavain was shown to have a high affinity to glycine receptors and also acts as an antagonist, similar to strychnine. Researchers theorize that kava lacks toxicity similar to strychnine in this regard due to its ability to positively modulate GABA-A receptors as well.

Our facts of the day have covered positive allosteric modulation by kavain at the GABA-A receptor, and now we see kavain as a negative allosteric modulator at the target of glycine receptors. “Allosteric'' in this sense means that kavain exerts its action by means other than binding to the orthosteric, or endogenous binding site of the glycine receptor. Similar to how benzodiazepines bind to allosteric sites on GABA-A, so it is thought that kavain may have its own set of specific sites at which to bind as well. These sites have yet to be discovered specifically for the glycine receptor.

What does this mean to the kava experience?

It may not mean all that much to the physical experience of kava, seeing that not only are glycine receptors affected, but also GABA-A receptors. Where glycine receptor antagonism would cause an increase in the possibility of the neuron firing and may increase excitability, GABA-A modulation from kava reduces this possibility and produces an overall calming effect. It’s possible that the concentration enhancing effects of kava at low doses may be a result of this, however more research in this area is needed.

In summary we can see that kava, specifically kavain, acts as a glycine antagonist. However, due to the way kava affects other receptors, this lacks the toxic effects normally seen by other glycine antagonists such as strychnine. Kava’s ability to compete with strychnine at the glycine receptor as well as it’s activity at GABA-A receptors reportedly alleviated its toxicity.


[1] Betz, Heinrich, and Robert J. Harvey. 2001. “Glycine as a Neurotransmitter.” In Encyclopedia of Life Sciences. Chichester: John Wiley & Sons, Ltd.
https://doi.org/10.1038/npg.els.0000140

[2] Palatnick, W., R. Meatherall, D. Sitar, and M. Tenenbein. 1997. “Toxicokinetics of Acute Strychnine Poisoning.” Journal of Toxicology. Clinical Toxicology 35 (6): 617–20.
https://doi.org/10.3109/15563659709001242

[3] Hj, Kretzschmar R. Meyer Hj. 1970. “Strychnine Antagonistic Potency of Pyrone Compounds of the Kava Root (Piper Methysticum Forst.).” Experientia 15 (26): 283–84.
https://doi.org/10.1007/BF01900097

[4] Hegazy, Nada Hany, Hans-Georg Breitinger, and Ulrike Breitinger. 2019. “Kavalactones from Kava (Piper Methysticum) Root Extract as Modulators of Recombinant Human Glycine Receptors.” Biological Chemistry 400 (9): 1205–15.
https://doi.org/10.1515/hsz-2019-0112
 

Orz[EST]

Kava Enthusiast
Glycine helps with sleep. I wonder if kavain occupies this receptor does it then antagonize sleep (in addition to noradrenaline reuptake inhibition).
 
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