Rhynchophylline, a Herbal NMDA antagonist

[dopamimetic]

Finally we have a candidate for a Natural Hole. Started an own thread for it because it's pretty unknown, in an earlier one about herbal dissos (which I can't find anymore, was January or so) the consent was there were none known yet.

"Rhynchophylline is an alkaloid found in certain Uncaria species (Rubiaceae), notably Uncaria rhynchophylla[1] and Uncaria tomentosa.[2] It also occurs in the leaves of Mitragyna speciosa (kratom),[3] a tree native to Thailand. Chemically, it is related to the alkaloid mitragynine.

Rhynchophylline is a non-competitive NMDA antagonist (IC50 = 43.2 μM) and a calcium channel blocker.[4][5]

Uncaria species have had a variety of uses in traditional herbal medicine, such as for lightheadedness, convulsions, numbness, and hypertension.[6] These uses have been associated with the presence of rhynchophylline and have encouraged its investigation as a drug candidate for several cardiovascular and central nervous system diseases; however, few clinically relevant studies have been conducted.[6] (wikipedia)"

At least it isn't inactive:

Rhynchophylline Protects Cultured Rat Neurons against Methamphetamine Cytotoxicity

Rhynchophylline (Rhy) is an active component isolated from species of the genus <i>Uncaria</i> which has been used for the treatment of ailments to the central nervous system in traditional Chinese medicine. Besides acting as a calcium channel blocker, Rhy was also reported to be able to protect...

www.hindawi.com

Seems to help with drug addiction and "has effects on sedation" so stimulating(?) -> Google Books

It is also contained in kratom but didn't find numbers, so hope it's only trace amounts there and Uncaria might be more potent. It doesn't need to provide a hole at all, I'd be very happy with effects similar to a low dosage of e.g. ketamine. Promising? Any more info?

 

[Neuroborean]

There was a thread somewhere, probably on reddit (?) that talks about using very high doses of uncaria tomentosa (cat claw's) which has little amounts of rhynchophylline and the guy got effects, probably light dissociative ones as I remember.

 

[izo]

i somehow doubt that its a good drug, but a bioassay would be interesting.

 

[Morbid Sea Cow]

Only one way to find out, any info on people trying to isolate it and ingest it themselves, outside of the context of clinical rat trials?

 

[Skorpio]

The IC50 of 43.2 micromolar is super high. It is unlikely that this concentration will be even approached by a tenth in a person taking any herbal preparation.

The paper from wiki which cited this also couldn't come up with a clear mechanism similar to known dissociatives. This compound likely presents in a manner unlike classic NMDA antagonists (in the unlikely case it reaches a high enough concentration at the neuron to do a damn thing).

From
Rhynchophylline and isorhynchophylline inhibit NMDA receptors expressed in Xenopus oocytes

These findings suggest that the alkaloids are able to specifically interact with the NMDA-subtype glutamate receptor. However, considering the fact that the suppressive effects of rhynchophylline and isorhynchophylline on NMDA responses were independent of membrane potential and agonist-use, it is unlikely that these alkaloids act as direct open channel blockers like MK801, PCP, ketamine and SKF-10,047 Burnashev et al., 1992, Mori et al., 1992, Yamakura et al., 1993. The present study revealed that rhynchophylline and isorhynchophylline suppress the NMDA response by decreasing the NMDA receptor efficacy (the maximal response) but not the NMDA potency (EC50). Interestingly, this mode of action was also true for the inhibition of the glycine response by the alkaloids: rhynchophylline and isorhynchophylline reduced the potency of glycine to enhance NMDA-activated currents without affecting the efficacy of the glycine site (EC50). Taken together with the fact that neither of the alkaloids showed an effect on the modulation of the NMDA receptor channel activity via the polyamine site, the redox site, the H+ site or the Zn2+ site, our findings raise the possibility that rhynchophylline and isorhynchophylline exert noncompetitive antagonism by allosterically inhibiting NMDA binding to the NMDA recognition site and/or glycine binding to the glycine recognition site on the NMDA receptor channel protein. Nevertheless, further investigation will be required to elucidate the site of action of rhynchophylline and isorhynchophylline on the NMDA receptors.

 

[allone]

its present in kratom. not sure how much tho, and if it does anything at all. the other potent alkaloids overshadow it. but assuming it is there in serious amount, it definately doesnt help against addictions, as i require more alcohol and cigarettes than ever on the kratom.