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Is l-theanine NMDA antagonist or agonist?

R

Renald

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Jul 8, 2015
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Have read several articles and discussions, and still do not understand is theanine agonist or antagonist ?
 
according to ME and MY experiments, neither. NOTHING. this shit probably works for little kids, try it
 
L-theanine wprls great in nootropic stacks mixed with caffeine. It allows you to harness the stimulation ftom caffeine but take the edge off. Its not super psychoactive but it is a great tool.
 
fwiw, phosphatidylserine was one of the few nootropic-touted supplements I tried and actually liked... you never know what is placebo, but it did stand out for me, made me feel more adequate mentally.

Also I love theanine, takes a while for the onset but then it relaxes me in a very benign and non-drowsy way. It may be an NMDA agonist but I sort of doubt that it reverses effects of NMDA antagonists like some nootropics can and also don't think that it implies glutamatergic excitotoxicity but that is perhaps because it antagonizes the kainate and AMPA subtypes? It is rather neuroprotective on its own. Maybe that means it is better to not try and induce glutamatergic effects of theanine that are otherwise limited, even if it's possible.
Seems feasible that e.g. agonizing kainate etc stronger than theanine antagonizes it may reverse its neuroprotective effects into potential glutamatergic issues?

Ampakines are apparently safer if you want cognitive enhancement via glutamate/accholine.
 
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Kainate agonists aren't something you want to fuck with in-vivo. Most likely effect of KAR-mediated excitotoxicity is, IMO, a long-lasting neurotocic allodynia and potentially very painful erythromelalgia. The nasty-as-shit acromelic acids (fungal biotoxins found in certain Clitocybe species, notably C.acromelalga (far east) and C.amnoelens (european) are orthosteric KAr agonists, and if these fungi are eaten the result of the poisoning manifests as a nonfatal but highly unpleasant allodynia and acromelalgia whereby damage to spinal neurons induces a very painful response, primarily erythromelalgia, and allodynia..., that worsens usually at night, especially in response to heat and can be temporarily relieved by immersing hands and feet in cold water. Sometimes also hepatorenal impairment although it doesn't take the fulminant course induced by amatoxin, orellanine (from toxic Cortinarius species, some of these have been responsible for occasional epidemics of poisoning and waves of fatalities) or the less severe but accelerated kidney failure brought on by allenic norleucine and/or chlorocrotylglycine from Amanita smithiana and A.proxima.

The allodynia syndrome due to KAr agonist excitotoxins is unusually longlived, sometimes persisting for years,
 
Very interesting, and message received - I won't be downing a glass of kainic acid anytime soon. Allodynic epilespy can't be fun, and the fucker outcompetes the wonderfully umamic glutamic acid on my tongue (it always does), ruining my anchovy-topped parmesan.

Fun to see those lowly kainateRs shifting some serious weight when they are really put to work. Some say they can fully substitute for AMPA receptors for LTP expression. Others say they're the modest type with tremendous talent and energy when the chips are down.

Or perhaps they're just hotheads.
 
I do wonder if there are allosteric regulatory sites on KARs (any kind) and what a positive allosteric modulator would do.

And never mind buggering with MSG if its umami you desire. Fly agaric is one my favourite spices in the kitchen (and the really neat thing is that Amanita muscaria has a parasite that is just as useful in its own, very different way. Its called Chalciporus piperatus, or the peppery boletus. Parasitic on fly agaric and when picked, dried for use and tossed in a spice grinder (better immediately before tossing some into a recipe its quite a fiery wee bugger, in its own unique way. Different from black pepper, chillies, Polygonum hydropiper (water pepper, a relative of the Bistort plant, and with fiery, biting hot leaves.) or stonecrop, a tiny little dry stone wall-loving plant with little roundish greenish-yellow juice-filled blebs that have a delayed, yet strong burning-biting heat. ) The peppery boletus like many of those other alternative gustatory prometheus-esque plants is in a class all of its own with regards to subtleties.

Fly agaric on the other hand is not hot or fiery, but once cured to convert the majority of the excitotoxin NMDA agonist to muscimol the traces that remain turn meat dishes from good chow into magic nosh fit to declare war over a few third or second-world countries over possession thereof, and of course, for the mushroom-picking rights.
 
I'd love to try some of those pepperants. I've seen loads of S. reflexum and other varieties but never thought of eating it, and I must look out for that boletus and its chalciporones.

A patent filed in the sixties seems keen on combining ibotenic acid with another compound which I didn't know, trichlomic acid, and they wax lyrical about the flavouring potential. Filed by Japanese, predictably. Perhaps a splash of enmushroomed Siberian reindeer urine will serve too.

Allosteric modulators of kainate receptors (some do exist) could be interesting to play with. A positive modulator, concanavalin A - a lectin from the Jack Bean plant, exists and is irreversible. The beans are toxic, but it's not obvious that concanavalin A is a contributor. Perhaps a negative one would be the kind of thing the guy in the pain thread is after, although I don't know of any.
 
I know what concanavalin-A is. And its nasty stuff. A haemagglutinin, similar to such things as the toxin from red kidney beans if uncooked. Haemotoxic, clots erythrocytes Its also a potent mitogen.

Tricholomic acid is dihydroibotenic acid. Would be interesting to try decarboxylation of it to yield dihydromuscimol.

Unfortunately unless the ibotenic acid/tricholomic acid were something available to the public, since the Trichs only grow in japan I'd have to get off my ass and start trying to knock some up.
And of the isoxazoles, thiomuscimol and its senenium analog interest me rather more.

An interesting fact about fly agaric-it contains MASSIVE quantities of vanadium, bound in a protein complex called amavadine. Don't think its known what it does or why the fungi bioaccumulate it. But its like that plant..whatssitnow...Bacopa monnieri I think, as a hyperaccumulator, both go nuts, although in the latter its primarily lead and cadmium, to a degree arsenic, Hg and other less than pleasant elements.

The only way you would want to or indeed should bugger about with concanavalin-A would be in cell culture. Thanks for reminding me about it actually, I've been looking for mitogens and mitotic inhibitors. Colchicine seems..difficult, as it thus far requires growing the plant over several seasons to get sufficient seeds to work with.
 
You are no stranger to a full strength muscimol / A. Muscaria trip then? Or do you only ever consume modest amounts for the cuisine..
 
I like fly agaric. I use it sometimes for psychotropic effects at time, for cooking, fresh, for eating as a table item as opposed to spicing meat and pot noodles up (especially nice with a splash of extra soy sauce and some worcestershire sauce in a chicken and mushroom one, once that disgusting corn is picked out.)

And its top notch as a medicinal...errr...herb???' as well.

Best thing to do with it is to use it to innure one to cold. It works brilliantly. Granted it won't physically protect you from hypothermia, but whilst on it, I've gone and walked a few miles in a howling blizard, bare chested and wearing only clothing below the waist. Didn't feel the slightest thing.

Tell you something though, a generous spoonful or two thrown into a chilli con carne, or a pinch mixed with a bit of salt on top of some thick, juicy grilled or fried sausages and I guarantee you will both start drooling, and take up hunting every year for as many carpophores as you can find.

Got bags and tupperware tubs filled to bursting with the dried mushrooms in the kitchen. Best way to consume it for an intoxicant or medicinally is to make a tea out of it, sweetened with some sugar, its weird, sweet but tastes like...kinda..concentrated, distilled pure essence of meat with meat sauce and extra meatyness.

It does however fill the kitchen with an INTENSE scent of sweetened, honey-ish umami.

Think akin to the result of leaving a jar full of chloroacetone out, only instead of tears and howling its MEAAAAT=D quite impossible to miss or ignore.

Don't use A.pantherina despite the similar biochemical profile. There are two excitatory aminoacid toxins in there, stizolobic and stizolobinic acid. These are either AMPA, KAR or both orthosteric agonists and they are of truly shocking, astonishing potency. So much so I did not even believe such a thing possible in a natural product that has not been specially optimized.
 
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I noticed that a village in northern Scandinavia had an unusual incidence of congenital pain insensitivity. Make that two things in their armoury then.

What's your preferred dose for cold-resistance (sub-psychotropic I trust)? I might take a pinch to the mountains to placate whingers.
 
Heh I hadn't thought of that. Wouldn't surprise me if the koryak and similar folks use it for that too. A few caps to a mug of tea. Depends on the potency of the caps, they vary widely.
 
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