15 replies to this topic

[Dom]

Does anybody know if there is any truth in this wikipedia page? What are your opinions on using anti-histamines as a nootropic?

The main reason I ask is that I have Asthma and I'm considering taking anti-histamines to see if it stops any potential allergic asthmatic triggers. If I could get a nootropic effect simultaneously it would be a bonus.

Anyone here in the know on H3 antagonists? Pros, cons, etc?

[StrangeAeons]

Part of modafinil's theorized MOA is in its effects on histamine. Additionally, the reason normal antihistamines are sedating appears to be due to their antagonism of H1/H2; the only reason drugs like Claritin are called "non-sedating" is their dosages being too low to be centrally active; this also means they are less effective.

[Dom]

Part of modafinil's theorized MOA is in its effects on histamine. Additionally, the reason normal antihistamines are sedating appears to be due to their antagonism of H1/H2; the only reason drugs like Claritin are called "non-sedating" is their dosages being too low to be centrally active; this also means they are less effective.

PetaKiaRose do you know if H3 antagonists would still have anti-inflammatory properties?

[Advanc3d]

An H3-receptor antagonist is a classification of drugs used to block the action of histamine on the Histamine H3 receptor. Unlike the H1 and H2 receptors which have primarily peripheral actions, but cause sedation if they are blocked in the brain, H3 receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine. Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H1 receptors in the cerebral cortex. Consequently unlike the H1 antagonist antihistamines which are sedating, H3 antagonists have stimulant and nootropic effects, and are being researched as potential drugs for the treatment of neurodegenerative conditions such as Alzheimer's disease.

NATURAL H3 ANTAGONIST

Conessine is a steroid alkaloid found in a number of plant species from the Apocynaceae family, including Holarrhena floribunda,[1] Holarrhena antidysenterica[2] and Funtumia elastica,[3] several of which are used in traditional herbal medicine as a treatment for amoebic dysentery.[4] It acts as a histamine antagonist, selective for the H3 subtype.[5]


so where would i get a H3 antagonist?

Edited by Advanc3d, 10 November 2008 - 01:22 AM.

[gizmobrain]

Any new info? It sounded promising in 2010:

Discovery of Histamine H3 Antagonists for the Treatment of Cognitive Disorders and Alzheimer's Disease

H3' class='bbc_url' title='External link' rel='nofollow external'>http://jpet.aspetjournals.org/content/336/1/38.abstract']H3 antagonists increase the release of brain histamine, acetylcholine, noradrenaline, and dopamine, neurotransmitters that are known to modulate cognitive processes. The ability to release brain histamine supports the effect on attention and vigilance, but histamine also modulates other cognitive domains such as short-term and long-term memory. A number of H3 antagonists, including 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine hydrochloride (BF2.649), (1R,3R)-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]cyclobutane-1-carboxamide (PF-03654746), 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254), MK-0249 (structure not yet disclosed), JNJ-17216498 (structure not yet disclosed), and ABT-288 (structure not yet disclosed), have advanced to the clinical area for the potential treatment of human cognitive disorders. H3 antagonists exhibited wake-promoting effects in humans and efficacy in narcoleptic patients, indicating target engagement, but some of them were not efficacious in patients suffering from attention-deficit hyperactivity disorder and schizophrenic patients. Preclinical studies have also shown that H3 antagonists activate intracellular signaling pathways that may improve cognitive efficacy and disease-modifying effects in Alzheimer's disease. Ongoing clinical studies will be able to determine the utility of H3 antagonists for the treatment of cognitive disorders in humans.

→ source (external link)

Edited by zrbarnes, 23 July 2012 - 08:24 PM.

[malden]

Ive orderd some betahistidine, if results are good i will post it here!

[gizmobrain]

Ive orderd some betahistidine, if results are good i will post it here!

Were they no good?

[malden]

Ive orderd some betahistidine, if results are good i will post it here!

Were they no good?

The quality of the pills are so bad, that i dont want to take it from this cource... i always order from this pharma but this time i dont now what to find about it.

-Edit its often priscribed off label for dizzy like symptoms, so to get is treu your first dok is easy i think

[Area-1255]

This should clear things up --> http://area1255.blog...mine-3-h3r.html

[Reformed-Redan]

Been there done that. Tried Pitolisant. Was a decent modafinil replacement without the long half life of modafinil. 

[Area-1255]

Been there done that. Tried Pitolisant. Was a decent modafinil replacement without the long half life of modafinil. 

Thioperamide certainly seems interesting. A novel adrenal cortisol blocker, H3/H4 antagonist....and nootropic / wakefulness aid - how much better can you get? Unfortunately, it's only R&D and is unlikely to be approved by the FDA anytime soon (if ever).

Thioperamide can potentially treat / cure many disorders because of it's strong anti inflammatory effect; it can effectively block histamine induced itching(   (which actually has more to do with H(4) than H(1)   ) - and allergies without producing a sedative effect. In other words, perfect modulation of histamine - taking full advantage of it's nootropic / vigilance promoting effects while minimizing / blocking the sides.

Edited by Area-1255, 28 August 2014 - 10:02 PM.

[Bateau]

This should clear things up --> http://area1255.blog...mine-3-h3r.html

 

Thanks for the writeup.

 

What dose of Kutaj do/did you take (mg would be helpful), what were the subjective effects and how long did they last?

 

Also what cyto/hepatotoxicity concerns do you think there are based off of these two studies?

 

There is a paucity of data on the occurrence of hepatotoxic and hepatocarcinogenic pyrrolizidine alkaloids in medicinal plants, and there are no data on the hepatotoxic properties of herbal medicines that are used in the traditional pharmacopoiea of Sri Lanka and other Asian and African countries. In view of the extensive consumption of these herbs and the occurrence of chronic liver diseases including hepatocellular cancer in this and other countries of South Asia, we have screened fifty medicinal plants for pyrrolizidine alkaloids and have obtained positive results with three species, namely Crotalaria verrucosa L., Holarrhena antidysenterica (L.) Br., and Cassia auriculata L. Feeding trials in rats with materials from these three species produced liver lesions--disruption of the centrilobular veins, congestion or haemorrhage in the centrilobular sinusoids, centrilobular or focal hepatocellular necrosis--and histopathology in the lungs and kidneys which were compatible with the action of pyrrolizidine alkaloids. The presence of alkaloids in C. auriculata has not been previously reported nor has the presence of pyrrolizidine alkaloids in H. antidysenterica. It is suggested that the consumption of herbal medicines that contain pyrrolizidine alkaloids could contribute to the high incidence of chronic liver disease including primary hepatocellular cancer in Asian and African countries.

→ source (external link)

 

Due to the slightly toxic nature (cytotoxicity = 14 μg/ml), biochemical analysis (liver function tests and kidney function test) of the serum of the mice after administration of conessine was also observed and is summarized in Table 4. In terms of pathogenesis, the host liver is among the organs affected in the early stage of malaria [28] leading to significant alterations in the host hepatocyte physiology and morphology. Elevated levels of ALP and bilirubin are an indication of hepatocyte damage due to malarial infection [29]. Acute renal failure or acute kidney injury and increased levels of creatinine and urea have been also associated with severe falciparum and vivax malaria [30]. Biochemical analysis of uninfected mice administered with the compound showed that conessine affected the function of the liver and kidney significantly as compared to normal mice (Table 4).

→ source (external link)

 

Table 4  shows great increase in urea and creatinine, and less but still significant increases in ALP and bilirubin

Edited by Bateau, 29 August 2014 - 12:13 AM.

[Area-1255]

 

This should clear things up --> http://area1255.blog...mine-3-h3r.html

 

Thanks for the writeup.

 

What dose of Kutaj do/did you take (mg would be helpful), what were the subjective effects and how long did they last?

 

Also what cyto/hepatotoxicity concerns do you think there are based off of these two studies?

 

There is a paucity of data on the occurrence of hepatotoxic and hepatocarcinogenic pyrrolizidine alkaloids in medicinal plants, and there are no data on the hepatotoxic properties of herbal medicines that are used in the traditional pharmacopoiea of Sri Lanka and other Asian and African countries. In view of the extensive consumption of these herbs and the occurrence of chronic liver diseases including hepatocellular cancer in this and other countries of South Asia, we have screened fifty medicinal plants for pyrrolizidine alkaloids and have obtained positive results with three species, namely Crotalaria verrucosa L., Holarrhena antidysenterica (L.) Br., and Cassia auriculata L. Feeding trials in rats with materials from these three species produced liver lesions--disruption of the centrilobular veins, congestion or haemorrhage in the centrilobular sinusoids, centrilobular or focal hepatocellular necrosis--and histopathology in the lungs and kidneys which were compatible with the action of pyrrolizidine alkaloids. The presence of alkaloids in C. auriculata has not been previously reported nor has the presence of pyrrolizidine alkaloids in H. antidysenterica. It is suggested that the consumption of herbal medicines that contain pyrrolizidine alkaloids could contribute to the high incidence of chronic liver disease including primary hepatocellular cancer in Asian and African countries.

→ source (external link)

 

Due to the slightly toxic nature (cytotoxicity = 14 μg/ml), biochemical analysis (liver function tests and kidney function test) of the serum of the mice after administration of conessine was also observed and is summarized in Table 4. In terms of pathogenesis, the host liver is among the organs affected in the early stage of malaria [28] leading to significant alterations in the host hepatocyte physiology and morphology. Elevated levels of ALP and bilirubin are an indication of hepatocyte damage due to malarial infection [29]. Acute renal failure or acute kidney injury and increased levels of creatinine and urea have been also associated with severe falciparum and vivax malaria [30]. Biochemical analysis of uninfected mice administered with the compound showed that conessine affected the function of the liver and kidney significantly as compared to normal mice (Table 4).

→ source (external link)

 

Table 4  shows great increase in urea and creatinine, and less but still significant increases in ALP and bilirubin

 

I took 3 grams of the whole powder, twice a day. Morphium is the best brand but it will ship from India.

 

I should warn you about buying whole powder, buy the Morphium capsules instead. 99% of people in the world will NOT be able to tolerate the taste of pure Kutaj diluted in water, it will make you throw up. Me, I am one of the few who can tolerate bitter, sickening powders. But I can guarantee for almost everyone who doesn't have a cast iron stomach (or titanium lol) - they will not be able to. Therefore stick with kutaj capsules from Morphium.

 

In regards to the effects, I noticed an enhanced sense of smell and focus, better pumps when working out (much better) and greatly increased strength (on bench press) - probably due to calcium channel enhancement caused by the alkaloids in Kutaj.

 

This includes the H3 blockade...which seems to give the perfect balance between stimulation and inhibition.

 

!***It also obliterated my appetite (usually eat 4 meals, ate two on this) and decreased need for water and hydration (expectedly, as histamine helps ration water)!***

 

I don't believe that it is that toxic, really not at all. I did see those studies but you have to realize the reference range and how it contrasts to humans. Also consider that mice have different liver function and respond differently even to histamine (as receptors in studies show) - in addition, with regard to any other study on the nootropic effects of H3 antagonists - always look for "In Vivo" or "In Vitro" - spliced cell studies have shown significant results to in tact cells in regard to histamine responses. This is consistent with the literature describing and contrasting differences between extracellular and intracellular histamine and / or Ca2+ channel output. In which case you dig further and find some regions of the brain in a mouse had significantly different responses in the guinea pig in regards to H3 in particular.

Edited by Area-1255, 29 August 2014 - 12:48 AM.

[Hip]

Been there done that. Tried Pitolisant. Was a decent modafinil replacement without the long half life of modafinil. 

 

Where did you manage to get some pitolisant, may I ask?

[Reformed-Redan]

 

Been there done that. Tried Pitolisant. Was a decent modafinil replacement without the long half life of modafinil. 

 

Where did you manage to get some pitolisant, may I ask?

 

From THT, when they were still up and running. 

[Area-1255]

 

 

Been there done that. Tried Pitolisant. Was a decent modafinil replacement without the long half life of modafinil. 

 

Where did you manage to get some pitolisant, may I ask?

 

From THT, when they were still up and running. 

 

IDK what the hell they're doing, starting to irritate me.