Inosine As A Powerful Inhibitor Of Serotonin And Cortisol Synthesis

[PhilParma]

Okay, thanks for your help. Love you guys.

 

[Texon]

I used it temporarily during a period of experiencing sudden breathlessness, racy heart and exercise intolerance in aikido. All the symptoms of elevated norepinephrine. I used inosine about 1 gram per day for about 2 wks. I know the feeling of adrenalin/NE. That course of inosine completely stopped the problem.
I no longer take it unless I do a hit of cardenosine.
To be honest, I think my adrenalin/NE are now flat-lined. But I am able to take T3 now with zero feelings of rT3.
I'm convalescing in Florida now and not training and holding onto my cardenosine for when I go back to training.
I still have not been able to reverse a lung issue and hoping living/sleeping with the windows open will resolve it. I'm at a loss what to do about my crappy lungs.
I've tried everything talked about on the forum.

Hi Regina...hope this is not a broken record, but have you ever tried Tianeptine or Guaifenesin (mucinex, aka the opera singer's friend)? I am taking the mucinex time release 600 mg tab X 2 per day as a trial for something not lung related. Only caution I can think of is it can very effectively lower blood sugar.

 

[Regina]

Hi Regina...hope this is not a broken record, but have you ever tried Tianeptine or Guaifenesin (mucinex, aka the opera singer's friend)? I am taking the mucinex time release 600 mg tab X 2 per day as a trial for something not lung related. Only caution I can think of is it can very effectively lower blood sugar.

Hey thanks Texon. I haven't tried it yet. But I just ordered some and will try the same dosage. Thx!

 

[nikkmm]

Hi Regina...hope this is not a broken record, but have you ever tried Tianeptine or Guaifenesin (mucinex, aka the opera singer's friend)? I am taking the mucinex time release 600 mg tab X 2 per day as a trial for something not lung related. Only caution I can think of is it can very effectively lower blood sugar.

I think you’re confusing Guaifenesin (mucinex) with Guanfacine. Guanfacine is the one you want for lowering noradrenaline.

1.-Guaifenesin is used in the treatment of cough; fibromyalgia; bronchitis; bronchiectasis and belongs to the drug class expectorants.

Read more at:
Guaifenesin Uses, Dosage & Side Effects - Drugs.com

2.-Guanfacine is used in the treatment of adhd; high blood pressure and belongs to the drug class antiadrenergic agents, centrally acting.

Guanfacine Uses, Side Effects & Warnings - Drugs.com

 

[lampofred]

I read somewhere that insoins functions as a natural benzodiazepine in our bodies. If so, it makes a lot of sense that it lowers serotonin and cortisol

 

[Texon]

I think you’re confusing Guaifenesin (mucinex) with Guanfacine. Guanfacine is the one you want for lowering noradrenaline.

1.-Guaifenesin is used in the treatment of cough; fibromyalgia; bronchitis; bronchiectasis and belongs to the drug class expectorants.

Read more at:
Guaifenesin Uses, Dosage & Side Effects - Drugs.com


2.-Guanfacine is used in the treatment of adhd; high blood pressure and belongs to the drug class antiadrenergic agents, centrally acting.

Guanfacine Uses, Side Effects & Warnings - Drugs.com

@Regina mentioned lung trouble so the suggestion for mucinex.

 

[Regina]

@Regina mentioned lung trouble so the suggestion for mucinex.

Hey Texon,
I did get to try the mucinex while I was in Florida. Definitely cleared some wheezing. I took it maybe for a week. Things really started to improve day by day in Florida; getting out working in the yard, sleeping with windows open. Then, my family installed the Reme-Halo induct air purifier in the HVAC with summer coming. That really is powerful.
I still have the fibrosis. But I think it's improved. I'm back in Chicago. The big test will be when I go back to aikido. Soon.
I've got the mucinex tablets you recommended ready.
Thx!

 

[Texon]

Hey Texon,
I did get to try the mucinex while I was in Florida. Definitely cleared some wheezing. I took it maybe for a week. Things really started to improve day by day in Florida; getting out working in the yard, sleeping with windows open. Then, my family installed the Reme-Halo induct air purifier in the HVAC with summer coming. That really is powerful.
I still have the fibrosis. But I think it's improved. I'm back in Chicago. The big test will be when I go back to aikido. Soon.
I've got the mucinex tablets you recommended ready.
Thx!

Great news! With all the junk in the air these days, it's a miracle we don't all have lung disorders of some kind.

 

[Nokoni]

inosine seems to have a VERY short half life, only minutes...

Maybe you were thinking of adenosine. "Adenosine has a short half-life (approximately 10s) and is rapidly deaminated to inosine, a stable metabolite with a half-life of approximately 15h."
The adenosine metabolite inosine is a functional agonist of the adenosine A2A receptor with a unique signaling bias. - PubMed - NCBI

 

[johnwester130]

inosine seems to have a VERY short half life, only minutes...

"
Inosine is an endogenous purine nucleoside that is produced by catabolism of adenosine. Adenosine has a short half-life (approximately 10 s) and is rapidly deaminated to i
inosine, a stable metabolite with a half-life of approximately 15 h. "

is that true

 

[Bart1]

I hope someone could shine some light on this. I thought I did well on inosine, my muscle weakness definitely got less, but do I understand correctly that it's a mast cell liberator, I have issues with mast cell activation and I'm wondering if this makes things worse

Inosine binds to A3 adenosine receptors and stimulates mast cell degranulation.

We investigated the mechanism by which inosine, a metabolite of adenosine that accumulates to > 1 mM levels in ischemic tissues, triggers mast cell degranulation. Inosine was found to do the following: (a) compete for [125I]N6-aminobenzyladenosine ...

www.ncbi.nlm.nih.gov

On the other hand I see an older study, talking about the inhibition of histamine release

Study of the inhibition of histamine release by inosine pranobex - Inflammation Research

The effects of Inosine pranobex and its parent compounds inosine and dimethylamino-2-propanol-p-acetamidobenzoic acid (DipPacBa) on the Concanavalin A (ConA)-induced histamine release from human adenoidal mast cells were investigated.Inosine pranobex inhibited the ConA-induced histamine release...

link.springer.com

I'm confused

 

[Dave Clark]

I hope someone could shine some light on this. I thought I did well on inosine, my muscle weakness definitely got less, but do I understand correctly that it's a mast cell liberator, I have issues with mast cell activation and I'm wondering if this makes things worse

Inosine binds to A3 adenosine receptors and stimulates mast cell degranulation.

We investigated the mechanism by which inosine, a metabolite of adenosine that accumulates to > 1 mM levels in ischemic tissues, triggers mast cell degranulation. Inosine was found to do the following: (a) compete for [125I]N6-aminobenzyladenosine ...

www.ncbi.nlm.nih.gov

On the other hand I see an older study, talking about the inhibition of histamine release

Study of the inhibition of histamine release by inosine pranobex - Inflammation Research

The effects of Inosine pranobex and its parent compounds inosine and dimethylamino-2-propanol-p-acetamidobenzoic acid (DipPacBa) on the Concanavalin A (ConA)-induced histamine release from human adenoidal mast cells were investigated.Inosine pranobex inhibited the ConA-induced histamine release...

link.springer.com

I'm confused

The second study says that, 'inosine itself enhanced histamine release', so I think they are both saying that inosine 'itself' does that. Question to me is always, what mitigates, and what cofactors enhance histamine release? In the second study when something else was added, no histamine release. So, in those terms, what foods or nutrients release histamine on their own, but maybe 'don't' when taken/eaten with other things? B1 is a histamine releaser to some people, and 'not' to others. I think it is an individual response dependent on other conditions and factors.

 

[Bart1]

yeah that’s always good to consider. As with thiamin a theory could be that it requires the other b’s and minerals, probably the same here, when metabolism is raised you need more nutrients otherwise you run into trouble

 

[NewACC]

As many of you know, I have been reading older Russian studies on many of the substances Peat talks about. He mentioned inosine in one of is articles, but only in relation to improving immunity and preventing dementia.
The problem of Alzheimer's disease as a clue to immortality Part 1
"...Adenosine: Sleep inducing protective effect. Adenosine is structurally very similar to inosine, another natural substance (found in meat, for example) which is a component of "inosiplex," an antiviral drug (Brown and Gordon, Fed. Proc. 29, 684, 1970, and Can. J. Microbiol. 18, 1463, 1972) or immunostimulant which has also been found to have an anti-senility effect (Doty and Gordon, Fed. Proc. 29). Adenosine is a free radical scavenger, and protects against calcium and glutamate excitotoxicity. (I. Yokoi, et al., "Adenosines scavenged hydroxyl radicals and prevented posttraumatic epilepsy," Free Radical Biol. Med. 19(4), 473-479, 1995; M. P. Abbracchio, et al., "Adenosine A(1) receptors in rat brain synaptosomes: Transductional mechanisms, efects on glutamate release, and preservation after metabolic inhibition," Drug Develop. Res. 35(3), 119-129, 1995.) It also appears to protect against the relative hyperventilation that wastes carbon dioxide, and endotoxin can interfere with its protective action. Guanosine, in this same group of substances, might have some similar properties. Thymidine and cytidine, which are pyrimidine-based, are endogenous analogs of the barbiturates, and like them, they might be regulators of the cytochrome P450 enzymes. Uridine, in this group, promotes glycogen synthesis, and is released from bacteria in the presence of penicillin."

Inosine is a component of a number of Russian drugs that were developed in the 1960s and 1970s and the most commonly used one is cytoflavin. Inosine is known as a potent cardioprotector and has been shown (in Russian studies) to prevent and reverse heart failure, and its main use in Europe today remains as a immunostimulant and cardioprotector. It inhibits lipolysis, increases glucose oxidation, increases mitochondrial biogenesis, and is considered an actoprotector - a substance that increase physical performance. Unfortunately, inosine got bad press in the Western world as a few studies with short-term (or even single) dosing showed no performance improvements. The full effects of inosine as an anabolic agent are visible after 30-60 days and most of those effects come from its ability to restore (or even increase) ATP levels. Inosine is breakdown product of ATP but there is the so-called purine salvage pathway, which can convert inosine back to adenosine->AMP->ADP->ATP.
I will make a more detailed review of inosine in another thread, but two studies that caught my eye were the ability of hypoxanthine (an immediate byproduct of inosine when taken orally) to potently lower serotonin synthesis/release. The study was in humans and used 1g hypoxanthine x 3 daily. The same dose of inosine should have comparable effects, but older studies with power lifters (especially in Bulgaria, Hungary and other Eastern Block countries) have used a dose of up to 50mg/kg (human dose) daily in divided doses. The second study shows that one of the likely mechanism of actions of hypoxanthine (and thus inosine) is a fairly selective MAO-B inhibition, which results in elevated dopamine levels. The HED from the second study (animal) matches quite well the 1g x 3 daily human dose from the first study, but it also shows that hypoxanthine doses as low as HED 2mg/kg (25mg/kg for mice) work too. MAO-B inhibitors have been shown to extend maximum lifespan in all animal models tested so far and the MAO-B inhibitor selegiline (Selegiline - Wikipedia) is a (ab)used by athletes and celebrities as an anti-aging and performance enhancing drug. As such, selegiline is banned by IOC/WADA as a doping agent. Well, it looks like humble inosine may be able to offer a great deal of the same benefits for a fraction of the cost. I don't know if inosine has a similar mechanism of action to pCPA (Fenclonine) but it may be able to achieve the same effects.
The only drawback to inosine is its ability to raise uric acid, which can exacerbate gout and can increase risk of kidney stones. Interestingly, older Russian studies show that higher doses of inosine are less likely to raise uric acid because inosine is an inhibitor of xanthine oxidase, and thus impedes uric acid formation. As far as I can remember the IC50 of inosine for xanthine oxidase was 80 uM/L, and that should be achievable with doses of 500mg or higher.
Finally, given the well-known relationship between serotonin and cortisol, a chemical that lowers serotonin synthesis is expected to lower cortisol levels as well. The human study did find lower cortisol too, as expected. In fact, the drop in cortisol by the 10th day was by a whopping 62% - a decrease almost identically matching the 60%+ decrease in serotonin.

Reduced urinary serotonin excretion after intake of high doses of hypoxanthine. - PubMed - NCBI
"...Two healthy volunteers were treated with hypoxanthine 3 x 1 g and allopurinol 3 x 100 mg daily for 1 week. During this treatment serum oxypurine concentration and urinary oxypurine excretion increased as expected. No side effects were observed except for some mild daytime drowsiness and lethargy. Measurements of urinary serotonin (5-HT) excretion showed decreases to as much as 60% below initial values. Decreased urinary 5-HT excretion was also found in a patient with incomplete Lesch-Nyhan syndrome during treatment with high doses of hypoxanthine. His neurological symptoms improved slightly. The results suggest that high doses of hypoxanthine exert a nonspecific sedative effect on both patients with Lesch-Nyhan syndrome and healthy controls. The cause is probably a reduced synthesis or release of 5-HT."

"...This suggests that the source of the problem is far remote from the locus of 5-HT synthesis. However, the decrease of the 24h urinary 5-HT excretion in our patient with incomplete Lesch-Nyhan syndrome as well in the two healthy controls after treatment with high doses of hypoxanthine suggests that purine metabolites may reduce the synthesis or the release of 5-HT in different tissues."

"...Parallel increased plasma levels of 5-HT and cortisol have been found in patients at the beginning of surgery and a postoperative return to presurgery levels [5]. Our results in the patient with incomplete Lesch-Nyhan syndrome show that high doses of hypoxanthine have a sedative affect accompanied by decreased cortisol and 5-HT values in both blood and urine. It is well known that different kinds of stress lead to increases in the secretion of adrenocorticotropic hormone, cortisol, noradrenaline, histamine, and 5-HT. Sedative drugs, however, diminish the secretion of these stress hormones. Treatment with high doses of hypoxanthine has a nonspecific sedative effect not only in patients with incomplete LeschNyhan syndrome but also in healthy controls probably due to a reduction in 5-HT secretion. It was suggested (W. Nyhan personal communication) that in our particular case of incomplete Lesch-Nyhan syndrome (6.9% HGPRT activity) a slight increase of his HGPRT activity would reduce his neurological symptoms. Since patients with an activity as low as 7.2% did not show neurological symptoms [12], we sought to increase the HPRT activity of our patient through elevating his hypoxanthine concentration in the tissues, especially in the brain. Our additional results suggest that the positive effect of the hypoxanthine treatment was a general pharmacological rather than a specific effect. The results support the hypothesis [11] that purine metabolites are able to modulate the release or the synthesis of neurotransmitters.

[Inhibitory effect of hypoxanthine on monoamine oxidase activity]. - PubMed - NCBI
"...Hypoxanthine was demonstrated to have a dose-dependent inhibitory effect on type B monoamine oxidase (MAO-B) activity in liver and brain tissues, and slight inhibitory effect on type A MAO(MAO-A) activity when given orally to mice at doses of 25-500 mg/kg. When mice were given orally hypoxanthine 500 mg/kg, MAO-A and -B activities were all inhibited significantly 16 hours after administration, but the inhibitory action on MAO-A was weaker. Subcutaneous injection of the agent also produced obvious inhibition of MAO activity in the liver but no significant influence on MAO activity in brain tissue was observed. In vitro experiment showed that the action of hypoxanthine on MAO-B was competitive inhibition and that on MAO-A was competitive mixed with noncompetitive inhibition."

Hello, @haidut I am very encouraged by such a strong and systemic effect of inosion! I live in Ukraine, and here I can get access to inosion powder very cheaply and without a prescription. @haidut, I did some research and even after taking 6.5g of inosine, maybe for some huge doses, didn't feel any noticeable effects. You said that hypoxanthine is the main by-product of inosine metabolism, what is the approximate coefficient of this conversion, since at my weight for the existing inhibition of the same MAO enzymes, 6g of hypoxanthine would be required, and possibly 13g for very strong inhibition. So it would be interesting to know how much hypoxanthine I get, for example, after taking 6g of inosine?

 

[NewACC]

@haidut Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?

 

[Borz]

I used it temporarily during a period of experiencing sudden breathlessness, racy heart and exercise intolerance in aikido. All the symptoms of elevated norepinephrine. I used inosine about 1 gram per day for about 2 wks. I know the feeling of adrenalin/NE. That course of inosine completely stopped the problem.
I no longer take it unless I do a hit of cardenosine.
To be honest, I think my adrenalin/NE are now flat-lined. But I am able to take T3 now with zero feelings of rT3.
I'm convalescing in Florida now and not training and holding onto my cardenosine for when I go back to training.
I still have not been able to reverse a lung issue and hoping living/sleeping with the windows open will resolve it. I'm at a loss what to do about my crappy lungs.
I've tried everything talked about on the forum.

did the lung issue appear after the inosine use?

I just found one of adrenaline’s functions is:
“relaxation of smooth muscle in the airways to improve breathing”

 

[Regina]

did the lung issue appear after the inosine use?

I just found one of adrenaline’s functions is:
“relaxation of smooth muscle in the airways to improve breathing”

No. I was wheezing along with the breathlessness at that time.
The lung issues completely resolved after a month in Georgia mountains the June after the covid fiasco started.

I have been fine since. Literally zero lung issues or breathlessness. I live in Florida now and have a lot of energy and endurance.

 

[Borz]

No. I was wheezing along with the breathlessness at that time.
The lung issues completely resolved after a month in Georgia mountains the June after the covid fiasco started.

I have been fine since. Literally zero lung issues or breathlessness. I live in Florida now and have a lot of energy and endurance.

wow great. what was the altitude?

 

[Regina]

wow great. what was the altitude?

I think it was around 2200 ft in GA. I just walked around in those mountains and I got better everyday.
I'm at sea level now. But not noticing a degradation of energy.

 

[success23]

No. I was wheezing along with the breathlessness at that time.
The lung issues completely resolved after a month in Georgia mountains the June after the covid fiasco started.

I have been fine since. Literally zero lung issues or breathlessness. I live in Florida now and have a lot of energy and endurance.

Can you please tell me which brand have you been using?