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Histamine H1,H2,H3 Receptors; interaction with neurotransmitters & Endorcrine systems.

histamine endo endocrine systems histamine h1 histamine receptors interaction neurotransmitters

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#1 Area-1255

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Posted 04 September 2014 - 01:38 AM


Before anybody jumps to premature conclusions and assumes they know everything about histamine and the brain, let me assure you that nobody else has taken the amount of time I have taken to compile this in-depth and intricate list of histamine receptors and their function. It would take an average individual quite a while; sifting through sources and finding meaningful ones - and that's just the first part of it.

But because I have it so committed to memory, I am much easier able to find these things and reveal the deepest secrets in neuromodulation; partly in effort of creating a possible and alternative cure for many mental disorders. 

To be clear, I am not claiming this as the "master key" in unlocking untapped brain potential - but it is a very significant one - one outlined (but perhaps indirectly) in all aspects of human behavior.

 

 


Edited by YOLF, 31 May 2016 - 01:53 AM.

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#2 Nordmann

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Posted 04 September 2014 - 04:31 PM

Intriguing...

 

Currently googling histamine-rich foods, is there supplements that would be beneficial? 


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#3 Area-1255

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Posted 04 September 2014 - 05:35 PM

Intriguing...

 

Currently googling histamine-rich foods, is there supplements that would be beneficial? 

There are no foods that contain histamine, but there some that contain the precursor to histamine; Histidine.

Histidine is then taken up into preferential tissues/cells in the body, where it meets with the enzyme "HDC" ; histidine decarboxylase.

This enzyme transforms histidine into histamine.

 

Salmon, Whale, Mushrooms, Dairy Products, Chicken and Soy Protein Isolate are the largest sources of L-Histidine.

 

I've also gotten very strong vasodilatory effects when drinking soy isolate, but the whole soy protein makes me feel like shit and miserable due to the effects estrogen and DHT. Soy Isolate leaves the majority of those flavonoids out and helps create CNS effects by means of L-histidine.

 

In addition, you can supplement with Vitamin B12, P5P (Pyridoxal-5-Phosphate) and Folate; all of which will create a trend towards greater histamine relief.

In addition, you can order the herb "KUTAJ" (HollarhenaAntiDysenterica) which has stimulant (!) and nootropic effects and was previously discussed not only here but on other forums (!) (!); where it's impressive role in treating narcolepsy and other severe CNS - nerve disorders was explored in great optimism(!). Kutaj ; hollarhena ; is a histamine h3 autoreceptor antagonist - which means ultimately it promotes histamine release by shorting out the histamine negative feedback loop and regenerating the enzymes (HDC) for histamine synthesis. (!) (!) (!)

 

 


Edited by Area-1255, 04 September 2014 - 05:41 PM.

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#4 Nordmann

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Posted 04 September 2014 - 08:05 PM

I'm already supplement with phenylalanine,glutamine,valine,leucine,isoleucine,Arginine and even other. I say fu** it and just start taking proteinpowder in 1 serving frequently within the day. There are benefits with them all, and maybe they make me more balanced throughout. Maybe I even buy a Diet one with slow carb, Vitamin and minerals.
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#5 Area-1255

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Posted 04 September 2014 - 09:46 PM

I'm already supplement with phenylalanine,glutamine,valine,leucine,isoleucine,Arginine and even other. I say fu** it and just start taking proteinpowder in 1 serving frequently within the day. There are benefits with them all, and maybe they make me more balanced throughout. Maybe I even buy a Diet one with slow carb, Vitamin and minerals.

Protein is always good!


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#6 Area-1255

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Posted 11 September 2014 - 10:34 PM

Article updated. 

Also I am going to add H(4)R to this soon. Found some interesting stuff on it.


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#7 jerrybusey

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Posted 11 September 2014 - 11:24 PM

To what extent can histamine presence/release in peripheral tissue influence the histaminergic system in the brain? From what I understand histamine doesn't substantially cross the blood-brain barrier so to what extent and through what mechanism might elevated levels elsewhere in the body lead to, for instance, activity at the H3 receptors in the brain?


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#8 Area-1255

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Posted 11 September 2014 - 11:59 PM

To what extent can histamine presence/release in peripheral tissue influence the histaminergic system in the brain? From what I understand histamine doesn't substantially cross the blood-brain barrier so to what extent and through what mechanism might elevated levels elsewhere in the body lead to, for instance, activity at the H3 receptors in the brain?

Histamine definitely crosses the blood brain barrier, well, histidine does and converts into histamine. Histamine is very much so present in the central nervous system and almost all area's in the brain. It is one of the most important neuromodulators and should not be overlooked. Too little histamine and your dopamine production plummets and / or accumulates in the wrong areas...too much histamine and your dopamine and serotonin signaling is grounded, and you become a product of an overstimulated environment. 

 

However, I've been on both sides of the spectrum, with blood work to go with it. I can EASILY say that high histamine from a neurological standpoint feels better than low histamine - which by contrast low histamine seems to produce more anhedonia than high.

High Histamine and Low Histamine both feel like a rollercoaster, but low histamine I feel more shallow and almost callous.

 

Low histamine leads to an adrenaline dominant/sympathetic state - and corresponding adrenal fatigue, high histamine leads to parasympathetic dominance and adrenal fatigue the other way around (by depleting adrenaline stores rather than crashing from consistently high adrenaline). 

 

Both imbalances made me dependent on stimulants.

 

Low histamine I had poor concentration, and little motivation for really anything. 

 

High Histamine I am fueled with creative ideas and an overall zest for life and anything in it.

Low histamine I feel paranoid and superficial.

 

 


Edited by YOLF, 31 May 2016 - 01:54 AM.

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#9 Area-1255

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Posted 14 September 2014 - 12:54 AM

Also histamine interacts with NMDA and glutamate a whole lot.


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#10 medievil

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Posted 14 September 2014 - 04:37 AM

Extremely high doses of betahistidine, a weak h1 agonist and h3 antagonist togheter with that histamine precursor may be interesting, the addition of a h2 antagonist would increase h1 agonism.

 

Overall I'm not that interested in histamine modulation tough, it does interact with a lot of stuff but in a boring way and the effects would be limited.


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#11 Area-1255

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Posted 14 September 2014 - 02:10 PM

Extremely high doses of betahistidine, a weak h1 agonist and h3 antagonist togheter with that histamine precursor may be interesting, the addition of a h2 antagonist would increase h1 agonism.

 

Overall I'm not that interested in histamine modulation tough, it does interact with a lot of stuff but in a boring way and the effects would be limited.

Idk dude, some of the H3 antagonists I took felt pretty damn close to Meth when combined with caffeine. All anxiety faded and I had a sense of ultimate excitement and euphoria...!


Edited by Area-1255, 14 September 2014 - 02:10 PM.

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#12 medievil

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Posted 14 September 2014 - 02:35 PM

 

Extremely high doses of betahistidine, a weak h1 agonist and h3 antagonist togheter with that histamine precursor may be interesting, the addition of a h2 antagonist would increase h1 agonism.

 

Overall I'm not that interested in histamine modulation tough, it does interact with a lot of stuff but in a boring way and the effects would be limited.

Idk dude, some of the H3 antagonists I took felt pretty damn close to Meth when combined with caffeine. All anxiety faded and I had a sense of ultimate excitement and euphoria...!

 

Hmm interesting, which compounds and what doses?


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#13 Area-1255

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Posted 14 September 2014 - 03:13 PM

 

 

Extremely high doses of betahistidine, a weak h1 agonist and h3 antagonist togheter with that histamine precursor may be interesting, the addition of a h2 antagonist would increase h1 agonism.

 

Overall I'm not that interested in histamine modulation tough, it does interact with a lot of stuff but in a boring way and the effects would be limited.

Idk dude, some of the H3 antagonists I took felt pretty damn close to Meth when combined with caffeine. All anxiety faded and I had a sense of ultimate excitement and euphoria...!

 

Hmm interesting, which compounds and what doses?

 

Thioperamide and Conessine namely.

 

Conessine at 250 mg x 4 a day.

Did NOT sleep but holy shit - I felt like a Kid with Invincibility and Super Speed combined with Extreme Euphoria. Lmao


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#14 Bateau

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Posted 14 September 2014 - 03:18 PM


Conessine at 250 mg x 4 a day.

Did NOT sleep but holy shit - I felt like a Kid with Invincibility and Super Speed combined with Extreme Euphoria. Lmao

 

 

How did you get an accurate dose of conessine? I've got some Kutaj but I'm unsure what dose to take and you've warned that the taste is atrocious.


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#15 Area-1255

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Posted 14 September 2014 - 03:20 PM

 


Conessine at 250 mg x 4 a day.

Did NOT sleep but holy shit - I felt like a Kid with Invincibility and Super Speed combined with Extreme Euphoria. Lmao

 

 

How did you get an accurate dose of conessine? I've got some Kutaj but I'm unsure what dose to take and you've warned that the taste is atrocious.

 

It's NASTY. I'm able to handle it but you better drink it fast. Maybe take an anti-nausea pill. 

Dude I basically drank 60 Grams (almost an 100 G bag) to get high.

You also might be shitting your brains out, but it's worth it.

Keep in mind I was on an high protein diet. 

10 G twice a day = mild stim effect with Caffeine.

40G+ and you probably won't sleep.

60G+ with caffeine and you will be high as hell.


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#16 medievil

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Posted 14 September 2014 - 03:25 PM




Extremely high doses of betahistidine, a weak h1 agonist and h3 antagonist togheter with that histamine precursor may be interesting, the addition of a h2 antagonist would increase h1 agonism.

Overall I'm not that interested in histamine modulation tough, it does interact with a lot of stuff but in a boring way and the effects would be limited.

Idk dude, some of the H3 antagonists I took felt pretty damn close to Meth when combined with caffeine. All anxiety faded and I had a sense of ultimate excitement and euphoria...!
Hmm interesting, which compounds and what doses?
Thioperamide and Conessine namely.

Conessine at 250 mg x 4 a day.
Did NOT sleep but holy shit - I felt like a Kid with Invincibility and Super Speed combined with Extreme Euphoria. Lmao
Very interesting, thanks for the info, sounds like a possible good stimulant potentiatiom, strategy.
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#17 Area-1255

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Posted 14 September 2014 - 03:29 PM

 

 

 

 

Extremely high doses of betahistidine, a weak h1 agonist and h3 antagonist togheter with that histamine precursor may be interesting, the addition of a h2 antagonist would increase h1 agonism.

Overall I'm not that interested in histamine modulation tough, it does interact with a lot of stuff but in a boring way and the effects would be limited.

Idk dude, some of the H3 antagonists I took felt pretty damn close to Meth when combined with caffeine. All anxiety faded and I had a sense of ultimate excitement and euphoria...!
Hmm interesting, which compounds and what doses?
Thioperamide and Conessine namely.

Conessine at 250 mg x 4 a day.
Did NOT sleep but holy shit - I felt like a Kid with Invincibility and Super Speed combined with Extreme Euphoria. Lmao
Very interesting, thanks for the info, sounds like a possible good stimulant potentiatiom, strategy.

 

That's with the pure conessine from Sigma..if you are using Kutaj you need to estimate the minor 0.XX concentrations and you will need a lot more.

Keep in mind Conessine has very slow BBB clearance...and a long half life - so it builds up and will stay in your system long enough to cause insomnia,

but the effects are worth it. 

So consider it a legal "meth-run".

 

Also...

My theory (and based on some science published) is that

 

If you were to use conessine for a long enough time - like months. 

It would be expensive...

But you would basically end up knocking down H3R expression enough to cause chronic upregulation of H1 or HDC activity at the least.

 

This would be a feasible way to become "genetically enhanced".

 

In addition to maximizing hormone output...a clear consequence of higher histamine levels.

 

Plus a higher metabolism

 

I am warning you though - your APPETITE will be OBLITERATED on Conessine.

I had to choke down two meals a day, and that was harsh.


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#18 Bateau

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Posted 14 September 2014 - 03:31 PM

 

 


Conessine at 250 mg x 4 a day.

Did NOT sleep but holy shit - I felt like a Kid with Invincibility and Super Speed combined with Extreme Euphoria. Lmao

 

 

How did you get an accurate dose of conessine? I've got some Kutaj but I'm unsure what dose to take and you've warned that the taste is atrocious.

 

It's NASTY. I'm able to handle it but you better drink it fast. Maybe take an anti-nausea pill. 

Dude I basically drank 60 Grams (almost an 100 G bag) to get high.

You also might be shitting your brains out, but it's worth it.

Keep in mind I was on an high protein diet. 

10 G twice a day = mild stim effect with Caffeine.

40G+ and you probably won't sleep.

60G+ with caffeine and you will be high as hell.

 

 

Jesus that's an insane dose. Was that 60 grams all at once or split into 4 doses? How long did the effects last? How much Yamoa did you have to take to experience similar effects? I could ask so many god dam questions right now.

 


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#19 Area-1255

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Posted 14 September 2014 - 03:33 PM

 

 

 


Conessine at 250 mg x 4 a day.

Did NOT sleep but holy shit - I felt like a Kid with Invincibility and Super Speed combined with Extreme Euphoria. Lmao

 

 

How did you get an accurate dose of conessine? I've got some Kutaj but I'm unsure what dose to take and you've warned that the taste is atrocious.

 

It's NASTY. I'm able to handle it but you better drink it fast. Maybe take an anti-nausea pill. 

Dude I basically drank 60 Grams (almost an 100 G bag) to get high.

You also might be shitting your brains out, but it's worth it.

Keep in mind I was on an high protein diet. 

10 G twice a day = mild stim effect with Caffeine.

40G+ and you probably won't sleep.

60G+ with caffeine and you will be high as hell.

 

 

Jesus that's an insane dose. Was that 60 grams all at once or split into 4 doses? How long did the effects last? How much Yamoa did you have to take to experience similar effects? I could ask so many god dam questions right now.

 

Yeah, four doses throughout the day. I would not be able to drink that all at once bro.

Conessine has slow BBB clearance and a long half life - so you can afford to do it steadily.


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#20 Bateau

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Posted 14 September 2014 - 03:40 PM

 

 


 

That's with the pure conessine from Sigma..if you are using Kutaj you need to estimate the minor 0.XX concentrations and you will need a lot more.

 

 

 

You bought pure conessine for Sigma? Isn't it like $127.50 for 50 milligrams?

 

How much Yamoa did you have to take to get similar effects?


Edited by Bateau, 14 September 2014 - 03:41 PM.

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#21 Area-1255

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Posted 14 September 2014 - 03:48 PM

 

 

 


 

That's with the pure conessine from Sigma..if you are using Kutaj you need to estimate the minor 0.XX concentrations and you will need a lot more.

 

 

 

You bought pure conessine for Sigma? Isn't it like $127.50 for 50 milligrams?

 

How much Yamoa did you have to take to get similar effects?

 

No I had** a resource that is able to get it cheaper - not anymore. Lately I just use the Kutaj. Yamoa you don't need to take that much, but the product itself is more expensive.


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#22 jerrybusey

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Posted 14 September 2014 - 05:05 PM

 

Extremely high doses of betahistidine, a weak h1 agonist and h3 antagonist togheter with that histamine precursor may be interesting, the addition of a h2 antagonist would increase h1 agonism.

 

Overall I'm not that interested in histamine modulation tough, it does interact with a lot of stuff but in a boring way and the effects would be limited.

Idk dude, some of the H3 antagonists I took felt pretty damn close to Meth when combined with caffeine. All anxiety faded and I had a sense of ultimate excitement and euphoria...!

 

 

I've only tried one dose of pitolisant so far (I need to wait on some other health issues before giving it a full trial) but I found it quite stimulating at 10mg. I'm surprised there aren't more user reports on it considering that it has been available from a known domestic vendor for a few months. In my obviously extremely limited experience, it feels more like modafinil than amphetamine in that it provides a somewhat less focused boost of energy. Interestingly though, in one of its clinical trials for narcolepsy it was suggested that there might be synergistic effects between it and current treatments for narcolepsy (i.e. stimulants). While the bavisant trial for adhd provided only non-significant improvements in adhd symptoms, I'm curious what would be possible with low doses of both pitolisant and a conventional stimulant like dexamphetamine. For my purposes I need a big energy boost and only a slight boost in focus/motivation so this combo has potential. In any event it will be some time before I try it.


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#23 Area-1255

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Posted 14 September 2014 - 10:50 PM

 

 

Extremely high doses of betahistidine, a weak h1 agonist and h3 antagonist togheter with that histamine precursor may be interesting, the addition of a h2 antagonist would increase h1 agonism.

 

Overall I'm not that interested in histamine modulation tough, it does interact with a lot of stuff but in a boring way and the effects would be limited.

Idk dude, some of the H3 antagonists I took felt pretty damn close to Meth when combined with caffeine. All anxiety faded and I had a sense of ultimate excitement and euphoria...!

 

 

I've only tried one dose of pitolisant so far (I need to wait on some other health issues before giving it a full trial) but I found it quite stimulating at 10mg. I'm surprised there aren't more user reports on it considering that it has been available from a known domestic vendor for a few months. In my obviously extremely limited experience, it feels more like modafinil than amphetamine in that it provides a somewhat less focused boost of energy. Interestingly though, in one of its clinical trials for narcolepsy it was suggested that there might be synergistic effects between it and current treatments for narcolepsy (i.e. stimulants). While the bavisant trial for adhd provided only non-significant improvements in adhd symptoms, I'm curious what would be possible with low doses of both pitolisant and a conventional stimulant like dexamphetamine. For my purposes I need a big energy boost and only a slight boost in focus/motivation so this combo has potential. In any event it will be some time before I try it.

 

It's weird, I did feel a stim effect from Pitolisant but not like Thio or Conessine.


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#24 Area-1255

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Posted 16 September 2014 - 07:36 PM

Thioperamide seems to give me a better sense of mental clarity in some regards, more relaxed on THIO but more excited on Conessine. Which means that in terms of histamine enhancement, thio must be better at increasing histamine-induced GABA whereas Conessine's effects are H3 centered. Seems like H4's have the potential to excite the nervous system even though the majority of H4' histamine receptors are in the spleen and endocrine tissues.

I do know that betahistine made me itch my brains out but not Conessine or THIO.

http://www.ncbi.nlm..../pubmed/9379777


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#25 gaengineer

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Posted 17 September 2014 - 02:45 PM

Has anyone been following Irdabisant?  It's completed Phase I clinical trials through Teva in the Netherlands with good results (as put up in July).  That seems to be the most promising H3 antagonist to me. 


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#26 Area-1255

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Posted 17 September 2014 - 04:42 PM

Has anyone been following Irdabisant?  It's completed Phase I clinical trials through Teva in the Netherlands with good results (as put up in July).  That seems to be the most promising H3 antagonist to me. 

Interesting, haven't heard much about it myself. Will look into it though.


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#27 jerrybusey

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Posted 17 September 2014 - 05:29 PM

Has anyone been following Irdabisant?  It's completed Phase I clinical trials through Teva in the Netherlands with good results (as put up in July).  That seems to be the most promising H3 antagonist to me. 

 

What about it do you prefer to the H3 blockers that are further along (i.e. pitolisant, bavisant, etc.)?


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#28 gaengineer

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Posted 17 September 2014 - 05:59 PM

WRT irdabisant I'm still thinking it may promote wakefulness, which would help me get rid of the narcoleptic effects I've struggled with for years.  Pitolisant looks more promising, but again, that's in conjunction with sodium oxybate, which I haven't tried.  The trials require being refractory to all the major narcolepsy drug classes, I think; none of the amphetamine deriatives or prodrugs had any effect on me, and both ampakines (e.g. modafinil and amodafinil (sp)) were also ineffective. 

 

Well, I also have ADD.  Bavisant didn't prove to be effective in clinical trials for that designation in 2012, so I'm less positive about it; I'd like to be able to take something that would hit multiple targets. 


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#29 Area-1255

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Posted 17 September 2014 - 06:36 PM

WRT irdabisant I'm still thinking it may promote wakefulness, which would help me get rid of the narcoleptic effects I've struggled with for years.  Pitolisant looks more promising, but again, that's in conjunction with sodium oxybate, which I haven't tried.  The trials require being refractory to all the major narcolepsy drug classes, I think; none of the amphetamine deriatives or prodrugs had any effect on me, and both ampakines (e.g. modafinil and amodafinil (sp)) were also ineffective. 

 

Well, I also have ADD.  Bavisant didn't prove to be effective in clinical trials for that designation in 2012, so I'm less positive about it; I'd like to be able to take something that would hit multiple targets. 

Conessine is WAY stronger than pitolisant in that regard. Conessine is a potent H3 antagonist with slow BBB clearance, a long half life and additional properties - like alpha-2-antagonism and serotonin blockade.

Trust me, Conessine beats em all with the exception of Thioperamide.


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#30 jerrybusey

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Posted 17 September 2014 - 06:41 PM

I'm more eager for pitolisant if only because I want to see its phase III data related to safety since it is after all the furthest along and potentially first to market of this new class. Even if irdabisant sails through trials it will be many years before it comes to market.


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