Pharmacology of Leonurine (Dagga alkaloid) - adenosine reuptake inhibitor?

[basement_shaman]

I have been comparing the molecular structure of leonurine, the principal alkaloid from Wild dagga, Klip dagga etc. in order to find structural similarities with an existing drug with a known pharmacological profile.
I finally hit a gold mine: two of the existing adenosine reuptake inhibitors are basically two molecules of leonurine stitched together at the double amine tail (save for a hydroxyl group being substituted for by a methoxy group.)
Take a look!

Do you think my hypothesis that leonurine acts as an adenosine uptake inhibitor is complete bullshit, or could there be some truth to it?
Caffeine, an adenosine receptor competitive antagonist, should then antagonize the effects leonurine, which makes the hypothesis easily testable by bioassays. I just smoked myself retarded in wild dagga, and I'm now going to down a few glasses of cola. But my results will mean nothing scientifically, they will only be mildly interesting at best. Hopefully a real study will be carried out one day.

Edit: as additional circumstantial evidence for my hypothesis, leonurine has been shown to protect against all kinds of ischemias^{1 2}, which adenosine also does^{3 4}.

Source 1
Source 2

Source 3
Source 4

 

[immad]

Interesting proposition!

However, cola, if not diet, contains quite a bit of sugar, which could taint your experiment.

 

[ebola?]

Caffeine, an adenosine receptor competitive antagonist, should then antagonize the effects leonurine, which makes the hypothesis easily testable by bioassays.

I think that the primary hypothesis is sound, but you won't be able to adjudicate the matter via bioassays, as additive but contrary effects could 'feel' similar to truly counterpoised effects.

ebola

 

[negrogesic]

Hmmm.....similarities in carisoprodol and various carbamates come to mind (phenprobamate, perhaps being the most relevant to this discussion)....

In other words, I do not think your notion is "bullshit", however I have never toyed with this plant/isolate, so I can't attest to how they could compare subjectively. And, as ebola points out, even I could compare their subjective effects......

 

[pharmakos]

i have no idea on the pharmocological mechanism of action of Wild Dagga, but i just thought i would chime in in case there are any doubters--wild dagga really is active! it produces a nice buzz when smoked, but you've gotta have pretty fresh stuff though. i once had stuff that was harvested less than a month before hand and it was the bomb. [/non-ADD material haha]

 

[ProducedRaw]

Since Cannabidol agonises Adenosine receptors, is it fair to assume that smoking weed with Wild Dagga would have a synergystic effect? Or even that taking Wild Dagga with a strong sativa would mellow it out some?

 

[pharmakos]

Since Cannabidol agonises Adenosine receptors, is it fair to assume that smoking weed with Wild Dagga would have a synergystic effect? Or even that taking Wild Dagga with a strong sativa would mellow it out some?

weed + dagga did feel different to me than either one felt alone. my favorite back then was actually weed + dagga + blue lotus resin. doesn't blue lotus affect adenosine too? i never realized that was the possible mechanism of action of dagga. cool stuff.

 

[basement_shaman]

Since Cannabidol agonises Adenosine receptors, is it fair to assume that smoking weed with Wild Dagga would have a synergystic effect? Or even that taking Wild Dagga with a strong sativa would mellow it out some?

There definitely is some synergistic effect, but I can't subjectively tell if the tro drugs act at the same site, or if they act on separate sites.

negrogesic: I took a look at phenprobamate, and while I can see the similarity, I think that since the double-bound oxygen atom is further from the aryl group, it would have a drastically different pharmacology. Also, this drug has effects similar to barbiturates when overdosed, and has anxiolytic effects. It sounds more like it has affinity for GABA_A-receptors than anything else, which I, after countless bowls and joints of various dagga species, find hard to accept.

Ebola and immad: You're right. My experiment told me nothing. I just can't concentrate hard enough on the effects and get a proper "feel" for them as they swish around in my consciousness.

thenightwatch: blue egyptian water lily (Nymphaea caerulea, I take it this is what you mean by blue lotus) seems to have a pharmacology associated with dopamine receptor antagonism or perhaps partial agonism, but not anything to do with adenosine receptors.
However, there is a lot of interaction between the two receptor groups, and there could easily be downstream modulation of adenosine receptors by nuciferine and aporphine from blue water lily.

Cloning of adenosine receptors [...] showed that A2A receptors are closely associated with D2 receptors. Distinct functional interactions at several levels were discovered, and there is now strong evidence that A2A receptors are tonically active and modified by dopamine acting at D2 receptors

Source.

 

[pharmakos]

^^^ ah thanks. yeah weed + dagga + blue lotus extract was a really neat smoke... way more visual than any of them on their own. no actual visual movement a la psychedelics, but my visual acuity felt like it was through the roof.

 

[Charles Ferdinand]

Looking for an ARI? Try Carisoprodol (and maybe Meprobamate)
A VERY potent ARI.

 

[basement_shaman]

Looking for an ARI? Try Carisoprodol (and maybe Meprobamate)
A VERY potent ARI.

Wasn't really looking, I just noticed the structural similarities and used to to make guesses about leonurine's mechanism of action. Meprobamate looks interesting but it doesn't seem to share pharmacophore elements with the drugs I posted.

 

[negrogesic]

I apologize if my observation suggested that there was anything more than a casual relationship between these carbamates and leonurine. It was simply what came to mind....

Further, I fully agree that the activity of hypnotic carbamates extends well into GABAergic territory; I believe I started a thread on here a while back to discuss the rather unique pharmacology of these compounds. If I recall correctly, my question stemmed from the rather vague pharmacological classification of carisoprodol and meprobamate prevalent in medical literature (including many commonly used clinical handbooks). I may be incorrect, but I seem to recall one of these clinical handbook referring the (partial?) reversal of meprobamate's hypnotic or perhaps anxiolytic properties by means of naloxone (I could be easily mistaken, do not quote me on this).

Yet, carisoprodol and meprobamate (based on my own rather extensive trials) are oddities that are at best 'barb-like' (a better description would be 'qualonesque'; not much better). I must emphasize that carisoprodol is not the mere 'miltown-prodrug' as is so commonly described (a consequence of limited availability and perhaps limited interest in the class as a whole). Carisoprodol, while admittedly similar to meprobamate, possesses differences that go beyond what one could strictly attribute as metabolic-pharmacokinetic, etc, etc......

I believe I had a point relevant to the thread in all of this......(multi-tasking causality)

 

[basement_shaman]

Ah no need to apologize, I simply misunderstood the point of your post
Reversal by naloxone is interesting. Did you know that the analgesic effects of nitrous oxide can be reversed by naloxone as well? Perhaps some downstream opiod receptor regulation is occurring, making the receptors more sensitive to endogenous opioid peptides or something.

I have no personal experience with carisoprodol/meprobamate, methaqualone, or barbiturates, so I can't help you with the subjective comparison of the three classes. But your note that carisoprodol does not only act as a prodrug is interesting.

I don't know what your point was either, but the bulk of your post was interesting anyway so no harm done :D