Kanna, Sceletium Tortuosum Can somebody explain the mechanism of activity and SAR????

[aguythatlikessmoke]

Can somebody explain the molecule Mesembrine and Tortuosamine?
Speculated Mechanism of action and The structure activity relationship of the Alkaloids in Sceletium Tortuosum???
Pharmacology also!
Thank you

 

[tweex]

Mesembrine:
It increases levels of cAMP by inhibiting PDE4 (which breaks it down):
https://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate#Functions
It also increases extracellular serotonin by blocking SERT:
https://en.wikipedia.org/wiki/Serotonin_transporter#Function

Can't find as much info on the activity of Tortuosamine.

I'll let some one with more knowledge talk about SARs for alkaloids...

 

[Hammilton]

N-methyltortuosamine may be an opioid. No idea on activity, though. Interesting structure. There's a precursor to mesembrine in kanna without that extra ring that I think is an opioid but I haven't gotten a pure sample yet.

 

[sekio]

This paper is probably worth a read.

J Ethnopharmacol. 2008 Oct 28;119(3):653-63. doi: 10.1016/j.jep.2008.07.043. Epub 2008 Aug 8.
Sceletium--a review update.

It is probable that plants of the genus Sceletium (Mesembryanthemaceae) have been used as masticatories and for the relief of thirst and hunger, to combat fatigue, as medicines, and for social and spiritual purposes by San hunter-gatherers (historically referred to as Bushmen) and Khoi pastoralists (historically referred to as Hottentots) for millennia before the earliest written reports of the uses of these plants by European explorers and settlers. The oral-tradition knowledge of the uses of Sceletium by indigenous peoples has largely been eroded over the last three centuries due to conflicts with settlers, genocidal raids against the San, loss of land, the ravages of introduced diseases, and acculturation. Wild resources of Sceletium have also been severely diminished by over-harvesting, poor veld-management, and possibly also by plant diseases. Sceletium was reviewed almost a decade ago and new results have emerged substantiating some of the traditional uses of one of South Africa's most coveted botanical assets, and suggesting dietary supplement, phytomedicine and new drug applications. This review aims to collate the fragmented information on past and present uses, the alkaloid chemistry and pharmacological evidence generated on Sceletium.

More importantly:

https://www.ncbi.nlm.nih.gov/pubmed/21798331

J Ethnopharmacol. 2011 Oct 11;137(3):1124-9. doi: 10.1016/j.jep.2011.07.035. Epub 2011 Jul 20.
Pharmacological actions of the South African medicinal and functional food plant Sceletium tortuosum and its principal alkaloids.
[...]
The [ethanol extract of S. tortuosum] was a potent blocker in 5-HT transporter binding assays (IC(50) 4.3 μg/ml) and had powerful inhibitory effects on phosphodiesterase 4 (PDE4) (IC(50) 8.5 μg/ml), but not other phosphodiesterases. There were no cytotoxic effects. Mesembrine was the most active alkaloid against the 5-HT transporter (K(i) 1.4 nM), while mesembrenone was active against the 5-HT transporter and PDE4 (IC(50)'s<1 μM).

 

[aguythatlikessmoke]

Thanks a lot I will read through all of this.
I have used Sceletium and its extracts for depression and anxiety. People get different results but I can attest it has strong antidepressive effects on me.
I was always intrigued by its Pharmacology and suprised that something Herbal was this intense. For me Sceletium seems to be in a class a lot higher than that of St.johns wort and on par with Pharmaceutical Antidepressants if not better less Side effects.

 

[bob_arctor]

Aguythatlikessmoke: Interesting. Could you describe in what form, dosage and what kind of effects you have experienced from Kanna a little bit more in detail?

 

[aguythatlikessmoke]

Aguythatlikessmoke: Interesting. Could you describe in what form, dosage and what kind of effects you have experienced from Kanna a little bit more in detail?

I used powdered Kanna. Both Extracts which are on the order of times 10 to times 15 strength and just plain regular Kanna powder. The dosages anywhere from 500 mg to 2 grams Orally. And about 200-500 mg sublingually or chewing it with Gum.

Effects initially a rise in anxiety, and tension within the first hour after dosing usually subsides though i have noticed that my adrenaline levels and my insomnia is sometimes worse when doing Kanna . Physical stimulation. Relief of Mental fatigue and Physical Fatigue. Mood lift Moderate intensity. Positive outlook. Clearing of mind. Increased concentration. Euphoria Mild to Moderate. Stimulation Physical mental. Some slight psychedelic effects such as outdoors appearing brighter and more beautiful than usual, increased depth and intensity of colour, Chilled out feeling, social more talkative, Increased Physical endurance . Comparable to the come up on mushrooms. Like my hearing and my vision are sharper. Synergy with Alcohol, enhanced drunk.

 

[aguythatlikessmoke]

Its mentally and physically stimulating. So yea it has slight side effects such as low levels of anxiety etc. But what is weird is that it really lifts your mood and it can suppress appetite. I feel a more positive outlook too. And it is mildly psychedelic leading to effects such as enhanced colours, nature appears more beautiful .