Botanical NMDA antagonist? Cyperus articulatus, Searsia spp.

[Limpet_Chicken]

Found a couple of interesting plant species in the lit. that seem to possess NMDA antagonistic effects.

The first is Searsia, this genus contains at least two species possessed of NMDA antagonists, binding in an un- or possibly both uncompetitive and noncompetitive manner (the response to NMDA-activated NMDAr Ca++ channels was greater than towards the channel in the absence of NMDA or glutamate, which is a similar effect to that of memantine, where the drug requires activation of receptors prior to binding, and thus has a greater effect upon inhibition of calcium currents where an agonist ligand is bound at a concentration equal to that of maximal efficacy than when agonist is bound at a submaximal level or is absent)

Very interesting sounding plants. I may have to track some down if I can. There also may well be GABAa positive modulators present. Used traditionally in S.africa for epilepsy and anxiolytic reasons. S.pyroides and S.dentata are both active in an NMDA antagonistic manner. S.dentata extract (EtOH extract) resulted in a somewhat greater maximal inhibition of calcium currents at a given concentration than did S.pyroides and so would appear to either possess more of the same antagonist, a related compound or both.

DOI 10.1016/j.jep.2011.05.038
http://sci-hub.cc/10.1016/j.jep.2011.05.038 full text.

Anyone care to look over those patch-clamp and cell clamp traces and comment on whether or not my conclusion is accurate?
And what is meant by 'run down' effect of prolonged currents?

Will comment on Cyperus articulatus in a bit, given I've gotten some morphine in my system and I'm not feeling a bit crap (my docs surgery isn't open this monday it seems and I've 'accidentally' (accidentally on purpose that is) ended up with an entire extra script. Just when I needed some for my persuit of desomorphine)

 

[sekio]

It's all in vitro, so it's pie-in-the-sky stuff until someone does the ADMET crunching. Generally if it turns out to be a flavonoid or something else that's polar and easily metabolically mangled, it's a no-go as a drug. I note they don't do any ID of the ethanol extract.

As for C. articulatus - eating sedges? Really? What?

 

[Limpet_Chicken]

Yes, the Cyperus species has quite a long history of use in new guinea, and parts of the amazon basin, where it is known as one of the Borrochero, or Borrachera plants. This means, roughly 'intoxicator' or 'that which maddens'. Its frequently a term applied both to plants containing anticholinergic delirients such as Brugmansias and Daturas, as well as to ayahuasca plants of various kinds.

Interesting and seemingly quite extensive pharmacological properties.

Active portion is the rhizome, Its used and is seemingly effective, in treating epileptic seizures, anxiety, insomnia, it contains compounds that act like NSAIDs and has some confirmed constituents that are NMDA antagonists. In addition, its used in ayahuasca, as many but of course not each individual plant, are host to Clavicipitalean fungi, of Balansioid heritage. Some such sedges are known to produce ergot alkaloids, which ones, aside from one, ergopbalansine, I don't know although ergobalansine is listed in my copy of TGC..

Whilst I am still looking for a source of the Sersia species, I have found one for the Cyperus articulatus rhizomes; This was also used in the US for a time, as a proprietary relaxant. People reported strongly sedating, relaxing, anxiolytic and very euphoric states when taken at higher doses.

Looks like this one MAY be a winner. I'm willing to take one for the team and do a bioassay if anyone's interested in the results. I've always loved my NMDA antagnists in any case, and they seem like a most scarce class of drugs in the botanical world, the dissociatives.

Also, anyone know anything about an ubulawu (zulu shamanic medicines) herb by the name of Imphepho? Helichrysum odoratissimum. I've a source for this, and for its essential oil. Traditionally either drunk as a tea, for lesser potency effects, or when smoked it induces 'overwhelming ensations of relaxation and stupor begin to take hold. Ethnographic reports cite firsthand accounts from the Shamans from the Lesotho region of South Africa, they describe being rapt into a hypnogogic state where dreams are experienced with alacrity and the clarity of normal consciousness. It is in this state of semi-consciousness that the shaman is able to communicate with the spirit world and receive the blessings and knowledge of past generations. They also report that as their body falls into a dream state they feel physically paralyzed, while their mind and memory remain intact and coherent, they claim that by maintaining this state of awareness over a period of time they were then able to enter the dream world with complete faculties and recollection.''

this is with the dried plant material, smoked. Since the actives, although I am not totally sure which ones are the euphoriants, are terpenoids apparently, bet they are rich in the essential oil.

Apparently NMDA antagonism, and it sounds quite similar to cannabinergic agonism in many respects.