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Natural NMDA antagonists

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Jamshyd

Bluelight Crew
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Hey all,

No, I am not asking for a dissociative that I can find growing on trees. lol.

What I am asking for is...

Are there any drugs or peptides found in nature that cause NMDA antagonism?

Of course, that is barring Ibogaine, Mg and Zn.

Any input would be appreciated.

I have searched a lot and couldn't find what I'm thinking about. I am aware though that I usually look in the wrong places :D

Again, I don't care if it gets you high or not - I am simply interested in naturally occuring compounds that are NMDA antagonists.
 
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Do a Pubmed search on "endopsychosin". That's the endogenous antagonistic ligand for the NMDA receptor and said to cause natural near-death experiences.

Then there's rhynchophylline:
http://www.ncbi.nlm.nih.gov/entrez/...d&dopt=Abstract&list_uids=15531384&query_hl=3

...and the essential oils from the rhizomes of Acorus gramineus:
http://www.ncbi.nlm.nih.gov/entrez/...d&dopt=Abstract&list_uids=11253173&query_hl=3

Finally, there's a plant growing in the mud along lakes. There is a Pubmed reference that its rizomes contain an NMDA antagonist. Unfortunately, I can't remember enough to find the abstract.
 
Endogenous... *looks it up* so it is... but at pretty small levels.

Histogranin is a peptide antagonist...
 
Here are a few papers that could be retrieved...

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Ions and amino acid analysis of Cyperus articulatus L. (Cyperaceae) extracts and the effects of the latter on oocytes expressing some receptors
Journal of Ethnopharmacology, Volume 95, Issues 2-3, December 2004, Pages 303-309
E. Ngo Bum, K. Lingenhoehl, A. Rakotonirina, H-R. Olpe, M. Schmutz and S. Rakotonirina

Extracts from rhizomes of Cyperus articulatus L. (Cyperaceae) used in Africa and Amazonia to treat many diseases has been shown to possess sedative and anticonvulsant properties. The aim of this study is to determine the mechanism of action of Cyperus articulatus extracts. In Xenopus oocytes expressing receptors, using electrophysiological measurement, extracts of rhizomes of Cyperus articulatus (300 ìg/ml) inhibited 50% of the EC50 and EC80 of glutamate (1.3 and 2.9 microM, respectively) induced inward current through hNMDAR1A/2A receptors. Extracts induced very small current through rGluR3 receptors. The largest current induced by the extract (30 mg/ml) represents 128% of the EC100 of glutamate induced inward current, through rGluR3 receptors. The excess 28% current could be induced by aspartate and/or glutamate in the extracts. The effect on Xenopus oocytes expressing heteromeric GABABR1b/R2 receptors and rectifying potassium channels (Kir3) is clear. A decoction and water extract of Cyperus articulatus induced a large inward current that represented 71 and 57% (respectively) of the EC100 of gaba (30 ìM) induced inward current. The water extract induced also a large current through rectifying potassium channels (Kir3). Part of the current induced through GABAB receptors could be related to rectifying potassium channels and GABAB site receptors. Cyperus articulatus extracts possessed components that could decrease excitation (NMDA receptor antagonists) and increase inhibition (GABAB receptor agonists) in the central nervous system.

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Protection of NMDA-induced neuronal cell damage by methanol extract of Zizyphi Spinosi Semen in cultured rat cerebellar granule cells
Journal of Ethnopharmacology, Volume 95, Issue 1, November 2004, Pages 39-45
Jeong Hee Park, Hyun Joo Lee, Sang Bum Koh, Ju Yeon Ban and Yeon Hee Seong

Zizypus is one of the herbs widely used in Korea and China due to the CNS calming effect. The present study aims to investigate the effect of the methanol extract of Zizyphi Spinosi Semen (ZSS), the seeds of Zizyphus jujuba Mill var. spinosa, on N-methyl-D-aspartate (NMDA)-induced neurotoxicity in cultured rat cerebellar granule neuron. ZSS, over a concentration range of 0.05–5 ìg/ml, inhibited NMDA (1 mM)-induced neuronal cell death, which was measured by a trypan blue exclusion test and a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay. ZSS (0.5 microg/ml) inhibited glutamate release into medium induced by NMDA (1 mM), which was measured by HPLC. Pretreatment of ZSS (0.5 microg/ml) inhibited NMDA (1 mM)-induced elevation of cytosolic calcium concentration ([Ca2+]c), which was measured by a fluorescent dye, Fura 2-AM, and generation of reactive oxygen species (ROS). These results suggest that ZSS prevents NMDA-induced neuronal cell damage in vitro.

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Celastrus paniculatus seed water soluble extracts protect against glutamate toxicity in neuronal cultures from rat forebrain
Journal of Ethnopharmacology, Volume 93, Issues 2-3, August 2004, Pages 213-219
Praful B. Godkar, Richard K. Gordon, Arippa Ravindran and Bhupendra P. Doctor

Aqueous extracts of Celastrus paniculatus (CP) seed have been reported to improve learning and memory in rats. In addition, these extracts were shown to have antioxidant properties, augmented endogenous antioxidant enzymes, and decreased lipid peroxidation in rat brain. However, water soluble extracts of CP seed (CP-WSE) have not been evaluated for their neuroprotective effects. In the study reported here, we used enriched forebrain primary neuronal cell (FBNC) cultures to study the neuroprotective effects of three CP-WSE extracts (a room temperature, WF; a hot water, HF; and an acid, AF) on glutamate-induced toxicity. FBNC were pre-treated with the CP-WSE and then with glutamate to evaluate the protection afforded against excitatory amino acid-induced toxicity. The criteria for neuroprotection were based on the effects of CP-WSE on a mitochondrial function test following glutamate-induced neurotoxicity. Pre-treatment of neuronal cells with CP-WSE significantly attenuated glutamate-induced neuronal death. To understand the molecular mechanism of action of CP-WSE, we conducted electrophysiological studies using patch–clamp techniques on N-methyl--aspartate (NMDA)-activated whole-cell currents in FBNC. WSE significantly and reversibly inhibited whole-cell currents activated by NMDA. The results suggest that CP-WSE protected neuronal cells against glutamate-induced toxicity by modulating glutamate receptor function.

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Effects of Cyperus articulatus compared to effects of anticonvulsant compounds on the cortical wedge
Journal of Ethnopharmacology, Volume 87, Issue 1, July 2003, Pages 27-34
E. Ngo Bum, A. Rakotonirina, S. V. Rakotonirina and P. Herrling

Cyperus articulatus L. (Cyperaceae) is a plant commonly used in traditional medicine in Africa and Latin America to treat many diseases. The water extract from rhizomes of Cyperus articulatus concentration-dependently reduced spontaneous epileptiform discharges and NMDA-induced depolarisations in the rat cortical wedge preparation at concentrations at which AMPA-induced depolarisations are not affected. The two antiepileptic compounds, valproate and ethosuximide, possessed effect neither on epileptiform discharges nor on AMPA- and NMDA-induced depolarisations. Phenobarbital, pentobarbital and phenythoin inhibited both AMPA- and NMDA-induced depolarisations and spontaneous epileptiform discharges. The effects of Cyperus articulatus were very close to the effect of -CPPene. -CPPene also inhibited spontaneous epileptiform discharges and antagonised NMDA- but not AMPA-induced depolarisations. The extract of Cyperus articulatus could contain components acting as NMDA antagonists.

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Anticonvulsant properties of the methanolic extract of Cyperus articulatus (Cyperaceae)
Journal of Ethnopharmacology, Volume 76, Issue 2, July 2001, Pages 145-150
E. Ngo Bum, M. Schmutz, C. Meyer, A. Rakotonirina, M. Bopelet, C. Portet, A. Jeker, S. V. Rakotonirina, H. R. Olpe and P. Herrling

The methanolic extract of rhizomes of Cyperus articulatus, a plant used in traditional medicine in Africa and Latin America for many diseases, possesses anticonvulsant activity in mice. This extract protected mice against maximal electroshock (MES)- and pentylenetetrazol (PTZ)-induced seizures. It also delayed the onset of seizures induced by isonicotinic acid hydrazide and strongly antagonized N-methyl--aspartate-induced turning behavior. The ED50 for protection against seizures was 306 (154–541) mg/kg intraperitoneally (i.p.) for the PTZ test and 1005 (797–1200) mg/kg i.p. for the MES test. The ED50 of methanolic extract against N-methyl--aspartate-induced turning behavior was 875 (623–1123) mg/kg i.p. C. articulatus L. methanolic extract protected 54% of mice from seizures induced by strychnine at the dose of 1000 mg/kg i.p. but had no or a moderate effect only against picrotoxin- or bicuculline-induced seizures. With these effects, the rhizome of C. articulatus L. possesses anticonvulsant properties in animals that might explain its use as a traditional medicine for epilepsy in Africa.

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Extracts from rhizomes of Cyperus articulatus (Cyperaceae) displace [3H]CGP39653 and [3H]glycine binding from cortical membranes and selectively inhibit NMDA receptor-mediated neurotransmission
Journal of Ethnopharmacology, Volume 54, Issues 2-3, November 1996, Pages 103-111
E. Ngo Bum, C. L. Meier, S. Urwyler, Y. Wang and P. L. Herrling

The marshland plant Cyperus articulatus (Cyperaceae) is commonly used in traditional medicine in Africa and Latin America to treat a wide variety of human diseases ranging from headache to epilepsy. We tested the hypothesis that the purported anti-epileptic effect of this plant might be due to a functional inhibition of excitatory amino acid receptors. One or several component(s) contained in the extracts inhibited the binding of [3H]CGP39653 to the NMDA recognition site and of [3H]glycine to the strychnine-insensitive glycine site of the NMDA receptor complex from rat neocortex. Water extracts from rhizomes of Cyperus articulatus dose-dependently reduced spontaneous epileptiform discharges and NMDA-induced depolarizations in the rat cortical wedge preparation at concentrations at which AMPA-induced depolarizations were not affected. We conclude that the purported beneficial effects of Cyperus articulatus might at least partially be due to inhibition of NMDA-mediated neurotransmission.
 
Cyperus articulatus is the lakeshore mud inhabiting plant I had in mind.
 
psychotria umbellata contains a purported nmda antagonist compound, or is it an agonist? do not remember. psychotria colorata apperantly has some opioid activity. could be a great combo.
I have been searching for some time, and even brazilian contacts have not found a thing.........
 
DXM is a NMDA antagonist, though not naturally occuring... I'm sure you already knew that though.

Can I ask why you're after such a compound? To combat amphetamine tolerance? Sedation?
 
what about magnesium? isnt this vitamin also an NMDA antagonist?
 
It's not a vitamin because vitamins are VITal AMINes.. and Magnesium isn't an amine. It's not REALLY an NMDA antagonist. Sure it blocks the NMDA receptor channel as normal voltages, but that's part of its normal function, it's non-competative... it's like saying the inactivation gate of the sodium channel is a sodium channel antagonist.
 
As Bilzor said, Mg is not an NMDA antagonist in the way we think of of NMDA antagonists, ie. I don't think an excess of Mg would lead to dissociation or such.

That being said, I do take Magnesium supplements every morning and every night.

Vilocidex: I am looking for natural NMDA antagonists for three reasons. The first being that I find it interesting that such drugs are not as abundant in nature as psychedelics, simulants and (to some extent) opiates.

The second reason is that I've been using semi-daily sub-recreational doses (10-20mg, no more) of Ketamine and it has been the only thing that cures my severe chronic depression (I am suicidal), and it works like magic, and does not seem to be affected by tolerance to the recreational effects of the drug. Not only that, but I also find that it has a nootropic effect the next day - my long-term recall is amazing. (Very) Low doses of PCP also help, and although it can help for many days after the dose, it does have a few negative side-effects, and I also don't feel very comfortable using this drug regularly. DXM does not seem to be as effective, and has unpleasant side-effects. Nitrous does seem to be effective, but (as expected) only for a short period of time. It does have the same nootropic effect as Ketamine, but it is also very expensive.

Keep in mind that in all of the above, I am talking at doses that do not produce any recreational effects, and no excessive mood lift - just a complete (positive) change in the way I view life and the world.

Now, thanks to all the suggestions in this thread. Ever since I have read them, I found that Cat's Claw extract is readily available at a local health store, and have tried it. At the recommended dose (which of course does not take in mind its alleged NMDA antagonistic effects, since thats not its primary use), it does little. Actually I found it does absolutely nothing.

At double the recommended dose, it seems to have the same effect as DXM (anti-depressant wise). At higher doses it starts manifesting some weak dissociative signature, also similar to DXM, but I am happy with Ketamine as a dissociative of choice and will not be trying Cat's Claw "recreationally".

I am now starting to think that the antidepressant action of the drugs that worked is through their DA affinity...
 
I'm sorry this is off-topic, but can these types of products reduce or intensify the effects of NMDA drugs such as K and Nitrous.
 
I think that magnesium has potentiated several DXM adventures I have had recently, but then DXM is a strange bird anyway, and has many varying effects........
 
psychotridine (and related) - from psychotria colorata
endopsychosin(a + b) - in the brain
agmatine(L-Arg decarboxylated)
conantokins - SOME of the(non-deadly) peptides from cone snails
xenon - RARE and expensive elemental gas
dextromorphine - kinda synthetic, it's (1 side/isomer) of the morphine molecule
some peptides of joro spider/egyptian digger wasp IE:JSTX3, PHTX3
ibogaine - the only actual reasonably obtainable one, altho it produces so many other FX so u cant say it's a straight nmda antagonist, o well


So basically, they are out there. But ridiculously hard to obtaine/purify especially by any natural means. So the the average person who does not have butt loads of money to thro away on synthetically obtaining these or who doesn't have a PHD and tons of xpensiv equipment... the answer is NO
 
I recall a discussion on govteen.com recently, that lead to me looking up psychoactivity in mullberry species, supposedly, in the unripe fruit, the active compound is an NMDA antagonist, I can't remember its name off hand though (especially when I'm dead on my feet tired:p)
 
Magnesium will cause psychological effects in high doses, anaesthesia after that, and slightly further than that level you get a lot of organ/brain damage assumably through respiratory failure and hypoxia. I was privy once to a malpractice trial where a young male had been put under for a minor surgery and when she came to she was severely retarded to the point of disability. The cause seemed mysterious until you came across the anesthesiologist's notes; he'd accidentally administered an overdose of magnesium and this was the result.

Here is a study about it's use in dogs, from 1916. In the early 20th century it was sometimes used to anaesthesized humans for surgery; it became much less commonly used by itself thereafter.
 
Well, if I ever need to perform random surgery in the Urals, I can just shoot them up with milk of magnesia. who'd have thought.

Amazing that it works. Too bad about the side effects. Perhaps it'd be a decent recreational drug were it not for death.
 
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