LONGECITY

So i gathered from this site

http://www.wipo.int/...mp;DISPLAY=DESC

Antagonism at H3 receptor will

- Indirectly inhibits MAO
- Increase neurotransmitter release
- Inhibit diamine oxidase (Enzyme responsible to the break down of Histamine in the brain)
- Increase Brain Histamine thus,
- 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
- Betahistine is also a mild H1 agonist, further strengthening the above
- Significant reduction in symptoms of fatigue, via stimulant properties

and a lot more..
i shall give it a try.

So i gathered from this site

http://www.wipo.int/...mp;DISPLAY=DESC

Antagonism at H3 receptor will

- Indirectly inhibits MAO
- Increase neurotransmitter release
- Inhibit diamine oxidase (Enzyme responsible to the break down of Histamine in the brain)
- Increase Brain Histamine thus,
- 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
- Betahistine is also a mild H1 agonist, further strengthening the above
- Significant reduction in symptoms of fatigue, via stimulant properties

and a lot more..
i shall give it a try.

I asked my GP about this and he told me to just stick with modafinal b/c H3 antagonists seem to have a lot of interactions

So i gathered from this site

http://www.wipo.int/...mp;DISPLAY=DESC

Antagonism at H3 receptor will

- Indirectly inhibits MAO
- Increase neurotransmitter release
- Inhibit diamine oxidase (Enzyme responsible to the break down of Histamine in the brain)
- Increase Brain Histamine thus,
- 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
- Betahistine is also a mild H1 agonist, further strengthening the above
- Significant reduction in symptoms of fatigue, via stimulant properties

and a lot more..
i shall give it a try.

I asked my GP about this and he told me to just stick with modafinal b/c H3 antagonists seem to have a lot of interactions

if only i was able to get modafinil.
in australia it would be cheaper than anything but hard to request stuff like that just on the basis that i lack in motivation and such. especially since here we have health care cards that give medicine that is usually 20$ at something like $4 instead lol

20 dollars AUD for Modafinal?! Holy crap! I was looking at getting some modafinal and it was 179 dollars! So now I think I am just going to stick to adrafinal or amantadine.

also give HUGE weight loss

Did you ever give this a try? I was thinking of testing it out, though it becomes pretty expensive at the dosages suggested in the report(150-300mg/day).

I originally came across this report and then this thread after reading that Pfizer has a H3 Antagonist in Phase II right now for ADHD(PF-03654746). So, I'm wondering if there's any effect on ADHD.

Anyone?

High-dosage betahistine dihydrochloride between 288 and 480 mg/day in patients with severe Menière's disease: a case series.

Lezius F, Adrion C, Mansmann U, Jahn K, Strupp M.

Source

Department of Neurology, Klinikum Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany. franziska.lezius@med.uni-muenchen.de

Abstract

The objective of this study was to evaluate the clinical benefit and the side effects of high dosages of betahistine dihydrochloride (288-480 mg/day) in patients with severe Menière's disease (MD). In this case series 11 patients with MD who had not responded sufficiently to a dosage of 144 mg/day ofbetahistine dihydrochloride were treated on an individual basis with daily dosages between 288 and 480 mg of betahistine dihydrochloride. The number of attacks per month and the side effects were monitored. Non-parametric tests were used for statistical analysis. As a result, the frequency and the severity of vertigo were significantly reduced in all patients. The side effects were mild, self-limiting, and did not require any change in the treatment strategy. Despite the considerable limitations of an observational study--in particular in MD--high dosages of betahistine dihydrochloride between 288 and 480 mg/day seem to be effective in patients who do not sufficiently respond to lower dosages. Moreover, such dosages are well tolerated.

Its safe in those doses.

Its dirt cheap may give it a try in the future.

Effects of betahistine at histamine H3 receptors: mixed inverse agonism/agonism in vitro and partial inverse agonism in vivo.

Gbahou F, Davenas E, Morisset S, Arrang JM.

Source

Laboratoire de Neurobiologie et Pharmacologie Moléculaire, Centre de Psychiatrie et Neurosciences, Institut National de la Santé et de la Recherche Médicale, 2 ter Rue d'Alésia, 75014 Paris, France.

Abstract

We previously suggested that therapeutic effects of betahistine in vestibular disorders result from its antagonist properties at histamine H(3) receptors (H(3)Rs). However, H(3)Rs exhibit constitutive activity, and most H(3)R antagonists act as inverse agonists. Here, we have investigated the effects ofbetahistine at recombinant H(3)R isoforms. On inhibition of cAMP formation and [(3)H]arachidonic acid release, betahistine behaved as a nanomolar inverse agonist and a micromolar agonist. Both effects were suppressed by pertussis toxin, were found at all isoforms tested, and were not detected in mock cells, confirming interactions at H(3)Rs. The inverse agonist potency of betahistine and its affinity on [(125)I]iodoproxyfan binding were similar in rat and human. We then investigated the effects of betahistine on histamine neuron activity by measuring tele-methylhistamine (t-MeHA) levels in the brains of mice. Its acute intraperitoneal administration increased t-MeHA levels with an ED(50) of 0.4 mg/kg, indicating inverse agonism. At higher doses, t-MeHA levels gradually returned to basal levels, a profile probably resulting from agonism. After acute oral administration, betahistineincreased t-MeHA levels with an ED(50) of 2 mg/kg, a rightward shift probably caused by almost complete first-pass metabolism. In each case, the maximal effect of betahistine was lower than that of ciproxifan, indicating partial inverse agonism. After an oral 8-day treatment, the only effective dose of betahistine was 30 mg/kg, indicating that a tolerance had developed. These data strongly suggest that therapeutic effects of betahistine result from an enhancement of histamine neuron activity induced by inverse agonism at H(3) autoreceptors.

The problem with betahistine is it's oral bioavaliability sucks - and the half-life is roughly 3 hours which means you would have to keep taking it every 3 hours, that's an inconvenient dosing schedule in my book. Although repeated administration may cause H(3) downregulation, it is called into question how positive of an effect this will be considering the body compensates for the excess NT's running through the CNS by upregulating alpha-2-receptor and imidazoline function.

H(3)R's also interact with D(1), D(2) and adenosine. 

For example, taking Caffeine with BetaHistine over time, would result in a four-fold increase in D(2) receptor density, this is negative feedback to help lower the excessive cAMP levels and thyroid hormone that would pumped out by blocking PDE's and H(3)'s over time.

 

That all being said, H(3) blockers are under investigation for sleep-wake disorders and memory impairment, as well as dementia and depression.

 

Might wanna read some of my articles regarding this topic.

 

http://area1255.blog...mine-3-h3r.html

 

http://area1255.blog...t=1408892625677

 

http://area1255.blog...sturbing_5.html

 

Also should be worth pointing out that betahistine is NOT the only H(3)R blocker available.

There is an herbal remedy described in the first article there known as "YAMOA" which also contains H(3) blockers. It has antioxidant effects too.