Misc Akuamma (kratom's kissing cousin)

[Snafu in the Void]

Has anyone heard of this stuff Akuamma? Seems to have hit the market only recently. Apparently it is related to kratom and has a similar buzz to a relaxing red strain. I might try this stuff out.

"Akuammine (vincamajoridine[2]) is an indole alkaloid. It is the most abundant alkaloid found in the seeds from the tree Picralima nitida,[3] commonly known as akuamma, comprising 0.56% of the dried powder. It has also been isolated from Vinca major.[2] Akuammine is structurally related to both yohimbine, mitragynine and more distantly Voacangine, all of which are alkaloid plant products with pharmacological properties.

Pharmacology
Akuammine has antimalarial activity,[3] and may be the primary constituent of P. nitida seeds responsible for this activity.[4]

Akuammine is an opioid antagonist"

Curiously, it's an opioid antagonist? Maybe it's one of the other alkaloids that does it?

 

[G_Chem]

Interesting… I wanna try this. Here’s another thread on it too.

Akuammine and other Indolic Opioids

This morning while I was getting ready for work, I came across "Akuammine"- an indolic plant alkaloid from Picralima nitida. This particular alkaloid is a mu-antagonist. I haven't been able to find the structures of the other indole alkaloids present in this plant that are agonists...

bluelight.org

-GC

 

[NawdybyNature]

First time hearing of this. Very cool

 

[G_Chem]

“Akuammidine showed a preference for mu-opioid binding sites with Ki values of 0.6, 2.4 and 8.6 microM at mu-, delta- and kappa-opioid binding sites, respectively.”

Then another article I found on morphine..

“morphine-6-glucuronide Ki = 0.6 nM; morphine = 1.2 nM”

So it seems while Akuammine is an antagonist, Akuammidine has strong agonist affinity comparable to morphine for Mu.

I hope to see some BL’ers experimenting soon

-GC

 

[cdin]

i have some. have taken it but had a krat/ope habit at the time. now that i dont, maybe ill give it another swing in a month or two.

 

[Snafu in the Void]

I'm curious enough to order some tomorrow. Will report back.

I found a decent company that sells 20x extract pills, reviews seem legit and overall quite good with several claiming it's better than kratom

apparently it's incredibly bitter material so pills are recommended I guess

my only concern is how abusable it is, I'm extremely comfortable with kratom (that it won't make me sell my mattress at 3am)

 

[G_Chem]

I'm curious enough to order some tomorrow. Will report back.

I found a decent company that sells 20x extract pills, reviews seem legit and overall quite good with several claiming it's better than kratom

apparently it's incredibly bitter material so pills are recommended I guess

my only concern is how abusable it is, I'm extremely comfortable with kratom (that it won't make me sell my mattress at 3am)

Excited to hear some reports from you guys.

With the main alkaloid still being the antagonist it probably will be at least similar to Kratom if not less likely for abuse. I’m interested in it for using it in a way similar to low dose naltrexone, even if it can’t get someone high it still may have uses in lowering tolerance and immune functions.

Now if someone could figure out how to isolate the Akuammidine, then we may be in trouble. That sounds like a fun side project that could be extremely lucrative.

Great thread btw, I love learning of new psychoactives and this is one I’ve never heard of before!

-GC

 

[G_Chem]

Doing some research I found article showing blood concentration of Akuammidine in rats. Typically opiates of desire often have shorter durations. This one has an extremely short duration with a very quick drop in blood concentrations. By 2hrs blood levels are nearing 0 again. This opiate if isolated would likely be extremely addicting if it hits the right receptors.

Toxicokinetics of 11 Gelsemium Alkaloids in Rats by UPLC-MS/MS

Gelsemium elegans (Gardn. & Champ.) Benth. is a plant belonging to the genus Gelsemium (family Gelsemiaceae), and its main components are alkaloids. It is a Chinese traditional medicinal plant and notoriously known as a highly toxic medicine. ...

www.ncbi.nlm.nih.gov

Here’s another tidbit from an article..

“A team of the researcher isolated Akuammidine, rhaziminine, and tetrahydrosecamine from Rhazya stricta. Acute administration of the lyophilized extract of R. stricta resulted in a significant antidepressant-like effect in experimental animals.”

“Akuammidine, rhaziminine, and tetrahydrosecamine possible mechanism resulted in a biphasic effect on the MAOA inhibitory component of tribulin.”

Ali, B. H., Bashir, A. K., Tanira, M. O. M., Medvedev, A. E., Jarrett, N., Sandler, M., et al. (1998). Effect of Extract of Rhazya stricta, a Traditional Medicinal Plant, on Rat Brain Tribulin. Pharmacol. Biochem. Behav. 59, 671–675. doi: 10.1016/S0091-3057(97)00464-4

Another article with the binding info..

Opioid activity of alkaloids extracted from Picralima nitida (fam. Apocynaceae) - PubMed

Extracts of the seeds of Picralima nitida (fam. Apocynaceae) have been reported to have opioid analgesic activity. In this investigation, isolated tissue bioassays and radioligand binding assays have been used to determine the opioid activity of five alkaloids--akuammidine, akuammine...

pubmed.ncbi.nlm.nih.gov

Corbett, A. D., Menzies, J. R. W., MacDonald, A., Paterson, S. J. & Duwiejua, M. The opioid activity of akuammine, akuammicine and akuammidine: alkaloids extracted from Picralima nitida (fam. Apocynaceae). Br. J. Pharmacol 119, 334 (1996).

And more info…

“Akuammidine possesses anti-inflammatory and anti-asthmatic properties.”

This article shows graphs with various doses of Akuammine and Akuammidine, and rat nociception.

https://www.researchgate.net/figure/Effects-of-akuammine-and-akuammidine-in-mouse-models-of-thermal-nociception_fig5_345870533

And finally THE ARTICLE, goes over these “Akua” alkaloids affinity to many different receptors…

https://www.researchgate.net/publication/345870533_Isolation_and_Pharmacological_Characterization_of_Six_Opioidergic_Picralima_nitida_Alkaloids

For Akuammine; light 5-ht1a, medium 5-ht1d, light 5-ht2b, very light 5-ht5a, light Alpha2a, strong MOR, medium KOR, light SERT.

Akuammine seems to show similar anti-nociception to Akuammidine at twice the dosage, despite its MOR antagonist effects. I wonder if it’s affinity on various 5-HT receptors has any play on its analgesic effects?

-GC

 

[Skorpio]

“Akuammidine showed a preference for mu-opioid binding sites with Ki values of 0.6, 2.4 and 8.6 microM at mu-, delta- and kappa-opioid binding sites, respectively.”

Then another article I found on morphine..

“morphine-6-glucuronide Ki = 0.6 nM; morphine = 1.2 nM”

So it seems while Akuammine is an antagonist, Akuammidine has strong agonist affinity comparable to morphine for Mu.

I hope to see some BL’ers experimenting soon

-GC

Micromolar affinity is 1000 times weaker than nanomolar affinity.

If selective for opiate receptors versus other targets, it could be feasible still.

Also, comparing binding affinities between assays is a pretty sketchy practice. These are often calculated via displacement of a ligand, and both the choice of the ligand to displace, and other elements of assay design can greatly influence it. I read a paper the other day that used ketanserin and DOI to look at 5HT2a affinities of various 2cb/dob derivatives, and the two assays gave about a 5-fold difference (and this is work done by the same group, with the only difference the displaced ligand. Different labs will have results that can vary much more than that).

However, a thousandfold difference in affinity allows one to make the claim that akuammidine is likely a much weaker agonist than morphine (i would guess it falls somewhere between a hundred food weaker to ten thousand fold weaker).

Doing some research I found article showing blood concentration of Akuammidine in rats. Typically opiates of desire often have shorter durations. This one has an extremely short duration with a very quick drop in blood concentrations. By 2hrs blood levels are nearing 0 again. This opiate if isolated would likely be extremely addicting if it hits the right receptors.

Toxicokinetics of 11 Gelsemium Alkaloids in Rats by UPLC-MS/MS
Here’s another tidbit from an article..

“A team of the researcher isolated Akuammidine, rhaziminine, and tetrahydrosecamine from Rhazya stricta. Acute administration of the lyophilized extract of R. stricta resulted in a significant antidepressant-like effect in experimental animals.”

“Akuammidine, rhaziminine, and tetrahydrosecamine possible mechanism resulted in a biphasic effect on the MAOA inhibitory component of tribulin.”

Ali, B. H., Bashir, A. K., Tanira, M. O. M., Medvedev, A. E., Jarrett, N., Sandler, M., et al. (1998). Effect of Extract of Rhazya stricta, a Traditional Medicinal Plant, on Rat Brain Tribulin. Pharmacol. Biochem. Behav. 59, 671–675. doi: 10.1016/S0091-3057(97)00464-4

Another article with the binding info..

Opioid activity of alkaloids extracted from Picralima nitida (fam. Apocynaceae) - PubMed​

Extracts of the seeds of Picralima nitida (fam. Apocynaceae) have been reported to have opioid analgesic activity. In this investigation, isolated tissue bioassays and radioligand binding assays have been used to determine the opioid activity of five alkaloids--akuammidine, akuammine...

pubmed.ncbi.nlm.nih.gov
Corbett, A. D., Menzies, J. R. W., MacDonald, A., Paterson, S. J. & Duwiejua, M. The opioid activity of akuammine, akuammicine and akuammidine: alkaloids extracted from Picralima nitida (fam. Apocynaceae). Br. J. Pharmacol 119, 334 (1996).

And more info…

“Akuammidine possesses anti-inflammatory and anti-asthmatic properties.”

This article shows graphs with various doses of Akuammine and Akuammidine, and rat nociception.

https://www.researchgate.net/figure...-models-of-thermal-nociception_fig5_345870533

And finally THE ARTICLE, goes over these “Akua” alkaloids affinity to many different receptors…

https://www.researchgate.net/public...of_Six_Opioidergic_Picralima_nitida_Alkaloids
For Akuammine; light 5-ht1a, medium 5-ht1d, light 5-ht2b, very light 5-ht5a, light Alpha2a, strong MOR, medium KOR, light SERT.

Akuammine seems to show similar anti-nociception to Akuammidine at twice the dosage, despite its MOR antagonist effects. I wonder if it’s affinity on various 5-HT receptors has any play on its analgesic effects?

-GC
Click to expand...

It would be very interesting to see these compounds compared to mytraginine and friends. Especially the MOR fsk induced cAMP suppression assay (gets closest to a measure of efficacy), and the analgesia assays. 5 mg/kg for rodents is in the realm of 0.4 mg/kg when metabolic scaling equations are taken into consideration (the equivalent dose of morphine would be around 0.5 mg/kg).

 

[G_Chem]

Micromolar affinity is 1000 times weaker than nanomolar affinity.

If selective for opiate receptors versus other targets, it could be feasible still.

Also, comparing binding affinities between assays is a pretty sketchy practice. These are often calculated via displacement of a ligand, and both the choice of the ligand to displace, and other elements of assay design can greatly influence it. I read a paper the other day that used ketanserin and DOI to look at 5HT2a affinities of various 2cb/dob derivatives, and the two assays gave about a 5-fold difference (and this is work done by the same group, with the only difference the displaced ligand. Different labs will have results that can vary much more than that).

However, a thousandfold difference in affinity allows one to make the claim that akuammidine is likely a much weaker agonist than morphine (i would guess it falls somewhere between a hundred food weaker to ten thousand fold weaker).


It would be very interesting to see these compounds compared to mytraginine and friends. Especially the MOR fsk induced cAMP suppression assay (gets closest to a measure of efficacy), and the analgesia assays. 5 mg/kg for rodents is in the realm of 0.4 mg/kg when metabolic scaling equations are taken into consideration (the equivalent dose of morphine would be around 0.5 mg/kg).

Thank you, missed that lol. And appreciate the info on the ligand displacement methodology, I’ll admit pharmacology isn’t something I’m well versed in.

A thousand fold difference in affinity I’m assuming means the analgesic properties of these drugs are likely mediated by multiple receptors instead of simply opiate receptors.

-GC

 

[ChemicallyEnhanced]

"kissing cousin" - you called?

 

[Skorpio]

Thank you, missed that lol. And appreciate the info on the ligand displacement methodology, I’ll admit pharmacology isn’t something I’m well versed in.

A thousand fold difference in affinity I’m assuming means the analgesic properties of these drugs are likely mediated by multiple receptors instead of simply opiate receptors.

-GC

Not necessarily, if it is selective for mu receptors relative to its affinity to other receptors the higher affinity would just mean a higher dose is required for analgesia.

A promiscuous pharmacology could also very well explain its effects though.

 

[Anonymous Dissident]

.5g-4g of seeds (ground) provided little indistinguishable from placebo in this kratom addict in this dose range. I mean to do a write up once I worked up to what, in me is an active dose and had tried it at a few different doses after finding my base dose. I'll update this, or the other thread, as I gain experience. These titrations have occured with at least 5 days between doses.

 

[Snafu in the Void]

.5g-4g of seeds (ground) provided little indistinguishable from placebo in this kratom addict in this dose range. I mean to do a write up once I worked up to what, in me is an active dose and had tried it at a few different doses after finding my base dose. I'll update this, or the other thread, as I gain experience. These titrations have occured with at least 5 days between doses.

this website I'm scoping recommends 0.5-2g of their 20x extract to "evaluate tolerance" in new users. I suspect it's not nearly as potent as kratom in base form.

 

[G_Chem]

this website I'm scoping recommends 0.5-2g of their 20x extract to "evaluate tolerance" in new users. I suspect it's not nearly as potent as kratom in base form.

Ya I was checking that 20x too. I’m also considering trying a basic A/B extraction too.. Gotta get some seeds first.

I’ve seen mixed reports, it sounds like my initial assessment of short duration was correct from the people actually getting positive effects. Sounds less “motivating” then kratom but decent analgesia. I’ve heard the seeds analgesic effects are mainly mediated by kappa but that person could’ve been wrong.

-GC

 

[Xorkoth]

So it is an antagonist of mu? Yet people are comparing it to kratom in effects? Am I missing something?

 

[jasperkent]

I am intrigued.

 

[Snafu in the Void]

So it is an antagonist of mu? Yet people are comparing it to kratom in effects? Am I missing something?

the most prominent alkaloid is antagonist, but there is also a mu agonist in there as well causing the psychoactive effects, from what I understand

 

[Xorkoth]

Ah, makes more sense.

 

[G_Chem]

Yea it seems while the main alkaloid is a mu antagonist, another is a mu agonist.

My impression is much of the analgesia is from its overall effect with kappa, with lesser coming from mu and delta. Akuammine has decent antinociception despite it being a mu antagonist, I’m guess it’s cuz of kappa.

-GC