Histamine H(3) receptors regulate histamine release; especially in the central nervous system. As a result, H3 receptors inhibit the release of multiple neurotransmitters that histamine normally stimulates through other receptors - including GABA, Acetylcholine, Dopamine, Norepinephrine and Glutamate. As H(1) receptors play a large role in calcium channel / cholinergic input that leads to wakefulness and vigilance - blockade of H(1) may produce drowsiness and sedation, whereas blockade of H(3) receptors leads to more H(1) activity and thus a higher level of wakefulness. Thus H(3) antagonists can be used for narcolepsy and other vigilance disorders.(1)(2)
In addition, since more neurotransmitters will be sustained by H(3) blockade - this can represent a novel method for treating Alzheimer's and Dementia.
There are a few different natural, herbal H(3) antagonists.
One of them is known as
"Funtumia Elastica Bark" or herbal name
"Yamoa".
Yamoa contains a chemical known as
"Conessine" which directly antagonizes (and with great potency) the H(3) receptor. Leading to stimulation and awareness. Conessine being a
natural H(3)R blocker, can also increase general metabolism and reduce appetite; which may be helpful in promoting weight loss.
Since yamoa protects against peripheral effects of histamine, and tends to lower histamine elsewhere, this should ensure that histamine plays it's role in the brain without being active enough to cause itching, allergies and asthma.
Some people have reported headaches from this supplement however - as well as a
slight increase in blood pressure; consistent with the
stimulating effects of Conessine.
Product can be bought below. It is an expensive product but I can vouch for both the stimulant effects and relief of allergies.
The second natural H(3)R antagonist is known as
Hollarhena Antidysenterica (Conessi bark or KUTAJ)
This herbal product also contains the same active substance "Conessine".
Although the concentrations are expected to be similar between this and Yamoa, it is hard to predict which one will be of higher potency.
Personally I have always felt that Kutaj has a stronger effect overall, but you also have to take MORE of it to get that effect. So you may be better off buying two bottles instead of one. Depending on your stimulant tolerance.
The concept of H3R antagonism is pretty new, and very interesting. If I recall correctly, they were studying Pitolisant for the treatment of Alzheimer's, Dementia and neuroprotection. Same with Thioperamide which happens to be in-dev anti-inflammatory / anti-itching and has protective effects on scopolamine induced memory impairment, as well as providing anti-seizure and anti-depressant effects. The effects on the classic "immobility time" test were quite impressive. I'll have to dig it up, but I'm sure if anyone - you already know about it Jay. You have been studying this a lot longer than I have.
ReplyDeleteYeah, I did quite a bit of research on it myself. Thioperamide is supposed to be the strongest out of all of them. Good luck getting your hands on it though! ;)
ReplyDeleteHello,
ReplyDeleteI read your post on longecity about H3-antagonist. Found the part with kutaj increasing strength due to calcium channel enhancement very interresting as I am competing. Coul you please guide me to some studies, etc regarding this aspect (kutaj, calcium channel enhancement, etc).
TY much!
Found a way to remedy the insomnia that it can cause? Any antagonistic herbs/neutraceuticals to offset this? The obvious ones are anti-histamines, but what about say GABA, magnesium, or Magnolia?
ReplyDeleteThis comment has been removed by the author.
DeleteCyproheptadine or other antihistamines should do the trick. Magnolia maybe a little. Aswagandha + L-Theanine is what I used to go to sleep on high-dose Conessine.
DeleteAwesome man. Yeah, I reckon Magnolia will do the trick for me. Well it proved to work last time. Today I've upped the dosage on Conessine. You should mention that Conessine displays strong binding to adrenergic receptors... What would this elicit? How would this shape the subjective experience?
DeleteCheers.
Conessine is an alpha-2-adrenergic antagonist so it raises Noradrenaline, Acetylcholine, Histamine etc through that pathway as well.
DeleteIt also mildly blocks Dopamine-autoreceptors, eliciting "extra" dopamine release.
--> https://www.ncbi.nlm.nih.gov/pubmed/18683917
I mean that Conessine is, IN ADDITION to a Histamine H3-antagonist/receptor blocker, an A2-antagonist and D2S-antagonist. :-)
DeleteVery interesting post, Thank you.
ReplyDeleteregarding the 'mind clarity' effect you report when using h3r antagonists
Do you have some dosing information with yamoa, kutaj vs pitolisant?