Betahistine

leokitten

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Betahistine has been mentioned in passing in various posts but I thought it would be useful to make a dedicated thread to discuss pharmacology and possible effect on ME symptoms.

Betahistine is typically prescribed for vertigo and other vestibular disorders. But in general it’s a strong H3 receptor antagonist, so it promotes the release of acetylcholine, histamine, dopamine, norepinephrine, serotonin, and GABA in the brain. It promotes arousal/wakefulness and is being studied or also prescribed for ADHD, atypical depression, and narcolepsy/EDS. It’s also a vasodilator in the brain and a weak H1 receptor agonist.

It’s generic and dirt cheap to buy at reputable online pharmacies. Any thoughts or experiences?
 
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leokitten

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Anything that promotes the release of histamines doesn't sound like a useful thing to me!
It’s a strong H3 receptor antagonist and these receptors are found primarily in the brain, so only promoting histamine release in the brain. It only has weak H1 receptor agonism. Also important to remember that the role of histamine in the brain is very different than its role in the body.
 
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A drug with similar H3 antagonist properties was approved recently for narcolepsy. You need to use about 100mg to 500mg to get results due to short half-life and low in-vivo potency. I recommend to use it along H1 antagonist to counter-act peripheral side effects. If you gave it a try let us know!
 

leokitten

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A drug with similar H3 antagonist properties was approved recently for narcolepsy. You need to use about 100mg to 500mg to get results due to short half-life and low in-vivo potency. I recommend to use it along H1 antagonist to counter-act peripheral side effects. If you gave it a try let us know!
Yes. pitolisant (Wakix) is an H3 antagonist recently approved for narcolepsy/EDS. But it’s a very expensive brand name drug and one of my points is why not use betahistine instead which has very similar properties and is dirt cheap to buy.
 

leokitten

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H3 antagonists and postoperative cognitive dysfunction. Krishnamurti. J Anaesthesiol (2019)
Since histamine (HA) was first synthesized in 1907 and isolated as a bacterial contaminant of an extract of ergot in 1910, its role in health and disease and its molecular mechanism of action have been unraveled, leading to the formulation of an array of drugs with immense therapeutic value. HA is produced by decarboxylation of histidine, and its biological actions are mediated through four HA receptors, namely, H1, H2, H3, and H4 based on their sequence, their link to differential intracellular signaling mechanisms, and their unique pharmacological properties. H1 and H2 receptors have been targeted for treating allergic conditions and peptic ulcers, respectively. The discovery of a third HA receptor subtype (H3R) by molecular biologists in 1983, structurally a member of the G-protein-coupled receptor family, has led to the development of many potent and selective H3 receptor antagonists having the potential to treat a wide spectrum of neurological diseases including postoperative cognitive dysfunction.
 

mitoMAN

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I have a narcolepsy specific Autoantibody and was wondering if Wakix could have potential use.
I'm pretty sure it can be sourced at a decent price with custom synthesis. I have stumbled across that drug long time ago when I was still under diagnosis for possible Narcolepsy (but ruled out then) and I dropped it.

Now the Nociceptin receptor Autoantibody popped up.
 

mitoMAN

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It’s a strong H3 receptor antagonist and these receptors are found primarily in the brain, so only promoting histamine release in the brain. It only has weak H1 receptor agonism. Also important to remember that the role of histamine in the brain is very different than its role in the body.
How would you suspect this for a patient with high MCAS? I generally suffer from extremly high histamine release found in serum and nothing really helped so far. Wondering if this could make things worse?
 

leokitten

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How would you suspect this for a patient with high MCAS? I generally suffer from extremly high histamine release found in serum and nothing really helped so far. Wondering if this could make things worse?
I would say the weak H1 receptor agonism that also acts peripherally isn’t ideal for pwMCAS. We don’t know how small the effect might be for each person, you’d have to try and see in order to know.

But the strong H3 receptor antagonism, where the H3 receptor is primarily found in the brain and acts only in the brain, so I don’t think there are any peripheral histamine effects. The H1-H4 receptors and histamine network in the brain modulate the release of many other neurotransmitters and function to control arousal/wakefulness and sleep.

So histamine has a very different role in the brain as a neurotransmitter than in peripheral tissues. Histamine also doesn’t cross the BBB. So overall I’m not sure how much the side effects would be for pwMCAS, but I would predict could be minor.
 

pattismith

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How would you suspect this for a patient with high MCAS? I generally suffer from extremly high histamine release found in serum and nothing really helped so far. Wondering if this could make things worse?
@leokitten

Maybe association with an histamine H1 antagonist would help?

I found this study with association of Cinnarizine + Betahistine helps for vertigo:

Cinnarizine/betahistine combination vs. the respective monotherapies in acute peripheral vertigo: a randomized triple-blind placebo-controlled trial - PubMed (nih.gov)

however, cinnarizin and others can have bad effects on movement disorders because they are dopamine D2 blockers

Cinnarizine- and flunarizine-associated movement disorder: a literature review | The Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Full Text (springeropen.com)

This antihistaminic maybe more interesting to test in association with Betahistine. It's a dopaminergic drug, which is the opposite to cinnarazine, and helps in Parkinson (a movement diorder).

Diphenylpyraline - Wikipedia
 
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pattismith

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https://doi.org/10.21203/rs.3.rs-143737/v1

]Histamine is a biogenic amine with high a nity for the H3 receptor, and has an important role in central nervous system functions, such as learning and memory.

]The H3 receptor has the role of releasing histamine from presynaptic neurons, and is a heterogeneous presynaptic receptor in the peripheral nervous system influencing the release of other neurotransmitters (dopamine and norepinephrine) (7).

It has been found that neurotransmitters, such as dopamine, norepinephrine, and acetylcholine play a key role in H3R improvement (8). Clinical studies have shown that potent and selective H3 antagonistes can be used as a novel therapeutic approach for different conditions, such as ADHD, Alzheimer’s disease, and schizophrenia (7, 9–11).

In addition, clinical models for treating ADHD have shown that increased synthesis of histamine and neurotransmitters through the histamine H3 receptor antagonist can effectively improve attention and reduce impulsivity (7, 12).

Conclusion: Betahistine plus Methylphenidate may be more effective in treating ADHD symptoms compared to Methylphenidate alone.
 

pattismith

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I am currently struggling with a Mirtazapine trial my psy doctor wants me to do....

Daytime sleepiness is one of my biggest problem, so needless to say that it's far worst with the mirtazapine...

I tried to increase the dosage to overtake the antihistamine sleepiness of this drug, but it didn't work...

So I had the idea to take a good amount of Betahistine and within a couple of hours I was suddenly awake!

Very interesting informations about Betahistine in this 2006 patent:

WO2007076140A2 - Treatment methods employing histamine h3 receptor antagonists, including betahistine - Google Patents
SUMMARY OF THE INVENTION
Accordingly, the present invention provides methods for treating diseases that involve symptoms relating to these central histamine systems. Generally, these disorders are characterized by disturbances of mood, cognition, arousal, appetite regulation, and disorders characterized by addictive behaviors or dysregulation of the hypothalamic- pituitary-adrenal (HPA) axis that would benefit from a therapy that enhances histaminergic neurotransmission.

Replacement Sheet One embodiment of the invention is directed to methods for treating depression. Certain subtypes of depression, including, for example, atypical depression and the depressive aspect of bipolar disorder, are particularly amenable to treatment according to the present methods. The methods comprise administering an effective amount of an (H3) receptor antagonist to an individual or patient in need thereof. An effective amount is an amount administered systemically, for example, orally, wherein the active crosses the blood brain barrier to impact central H3 receptors to increase histaminergic neuroactivity.

Another embodiment of the invention is directed to methods for treating a patient suffering from, recovering from, or predisposed to, one or more disorders selected from binge eating disorder, narcolepsy, excessive daytime sleepiness, substance use disorders, and Prader Willi syndrome. The method comprises administration of an H3 antagonist to the patient.
Betahistine has been shown to increase HPA activity in rats. Hence, betahistine, administered in doses which yield an effective central concentration, should benefit patients with atypical depression, and other patients with other illnesses associated with clinically significant hypocortisolism, such as fibromyalgia, chronic fatigue syndrome, autoimmune disorders such as rheumatoid arthritis and multiple sclerosis, somatoform pain disorder and post-traumatic stress disorder.
Further, given the link between the brain histamine system and reward and pleasure centers in the brain, as well as the evidence for altered histamine function in patients with alcoholism, betahistine therapy as described in this claim would help reduce excessive alcohol consumption.
etc etc