55 replies to this topic

[basileuz]

With new studies showing the possible efficacy of montelukast as a nootropic, I'm thinking of some experiments.

 

Has anyone ever tried montelukast and noticed nootropic effects?

 

 

http://www.theguardi...-study-suggests

http://www.longecity...nitive-decline/

[normalizing]

nobody else interested in this?

[MrSpud]

It's interesting. Can this compound be obtained otc anywhere?

Edited by MrSpud, 31 October 2015 - 06:34 AM.

[pleiotropic]

 

 

The drug did not improve the performance of young animals in the study.

 

Ah.  Not for the young ones among us then...

 

 

[gamesguru]

The original study:

Anti-inflammatory properties of montelukast, a leukotriene receptor antagonist in patients with asthma and nasal polyposis.
BACKGROUND: Leukotrienes, especially LTC4, are important inflammatory mediators in allergic and nonallergic inflammation of the entire airways. Of particular interest are numerous theories regarding the pathogenesis of aspirin intolerance with subsequent hyperproduction of leukotrienes and inhibition of cyclooxygenase.
OBJECTIVE: To examine the influence of the cysteinyl-leukotriene receptor antagonist montelukast on clinical symptoms and inflammatory markers in nasal lavage fluid in patients with bronchial asthma and nasal polyps, and determine its dependency on aspirin sensitization.
METHODS: Twenty-four patients (7 women, 17 men; median age, 55.5 years) with nasal polyps and controlled asthma (n=12 with aspirin intolerance) were treated with 10 mg montelukast once daily for 6 weeks in a blinded, placebo-controlled fashion. The placebo phase was randomly assigned 4 weeks before (n=12) or after treatment (n=12). Symptom score, rhinoendoscopy, rhinomanometry, smears for eosinophils, and nasal lavages for the determination of different mediators were performed.
RESULTS: Compared to placebo, there were significant improvements in the nasal symptom score and airflow limitation as well as a reduction in the inflammatory mediators in nasal lavage fluid after treatment. Furthermore, reduced eosinophils in nasal smears and peripheral blood were observed 2 and 6 weeks after treatment.
CONCLUSION:
Leukotriene 1 receptor blockade led to a significant decrease in eosinophil inflammation accompanied by a reduction in other mediators such as neurokinin A and substance P in the nasal lavage fluid of patients with nasal polyps and asthma, with or without aspirin intolerance.

Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug
As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood–brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias.

Inhibition of Leukotriene Receptors Boosts Neural Progenitor Proliferation
Neural stem and progenitor cells serve as a reservoir for new neurons in the adult brain throughout lifetime. One of the critical steps determining the net production of new neurons is neural progenitor proliferation, which needs to be tightly controlled. Since inflammation has detrimental effects on neurogenesis and the 5-lipoxygenase/leukotriene pathway is involved in inflammatory processes, we investigated the effects of leukotrienes and montelukast, a small molecule inhibitor of the leukotriene receptors CysLT(1)R and GPR17, on neural stem and progenitor cell proliferation. We demonstrate expression of the leukotriene receptor GPR17 by neural progenitors and by neural stem cells. Stimulation with excess amounts of leukotrienes did not affect progenitor proliferation, whereas blockade of GPR17 with montelukast strongly elevated neural stem and progenitor proliferation, while maintaining their differentiation fate and potential. This effect was associated with increased ERK1/2 phosphorylation suggesting an involvement of the EGF signaling cascade. Based on our results, montelukast and the inhibition of the 5-LOX pathway might be potent candidates for future therapies employing neurogenesis to promote structural and functional improvement in neurodegeneration, neuropsychiatric disease and ageing.

Montelukast, a cysteinyl leukotriene receptor-1 antagonist protects against hippocampal injury induced by transient global cerebral ischemia and reperfusion in rats.
Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory and immune modulating lipid mediators involved in inflammatory diseases and were boosted in human brain after acute phase of cerebral ischemia. The antagonism of CysLTs receptors may offer protection against ischemic damage. Therefore it seemed interesting to study the possible neuroprotective effect of Montelukast, a CysLTR1 antagonist in global cerebral ischemia/reperfusion (IR) injury in rats. Global cerebral ischemia-reperfusion was induced by bilateral carotid artery occlusion for 15 min followed by 60 min reperfusion period. Animals were randomly allocated into three groups (n = 30 per group): Sham operated, I/R control and rats treated with montelukast (0.5 mg/kg, po) daily for 7 days then I/R was induced 1 h after the last dose of montelukast. After reperfusion rats were killed by decapitation, brains were removed and both hippocampi separated and the following biochemical parameters were estimated; lactate dehydrogenase activity, oxidative stress markers (lipid peroxides, nitric oxide and reduced glutathione), inflammatory markers (myeloperoxidase, tumor necrosis factor-alpha, nuclear factor kappa-B, interleukin-6 and interleukin-10), apoptotic biomarkers (caspase 3 and cytochrome C), neurotransmitters (glutamate, gamma aminobutyric acid), Cys-LTs contents and CysLT1 receptor expression; as well as total brain infarct size and histopathological examination of the hippocampus were assessed. Montelukast protected hippocampal tissue by reducing oxidative stress, inflammatory and apoptotic markers. Furthermore, it reduced glutamate and lactate dehydrogenase activity as well as infarct size elevated by I/R. These results were consistent with the histopathological findings. Montelukast showed a neuroprotective effects through antioxidant, anti-inflammatory and antiapoptotic mechanisms.

Somatostatin inhibition of hippocampal CA1 pyramidal neurons: mediation by arachidonic acid and its metabolites
We used electrophysiological methods in a slice preparation to study the mechanisms of somatostatin (SS) effects on hippocampal pyramidal neurons. SS hyperpolarizes hippocampal pyramidal neurons in part by augmenting the time- and voltage-dependent M-current (IM), which has been shown to be reduced by muscarinic agonists. The SS effects are abolished by the phospholipase A2 inhibitors 4-bromophenacyl bromide and quinacrine. Arachidonic acid (AA) mimics all the effects of SS on hippocampal pyramidal neurons. The effects of AA and SS on IM are blocked by the lipoxygenase inhibitor nordihydroguaiaretic acid but not by the cyclooxygenase inhibitor indomethacin. Prostaglandins E2, F2 alpha, and I2 do not increase IM. However, the specific 5-lipoxygenase inhibitors 5,6-methanoleukotriene A4 methylester and 5,6- dehydroarachidonic acid both blocked the IM-augmenting action of either SS or AA. Leukotriene C4 (but not leukotriene B4) increases IM to the same extent as AA. IM was not altered by the 12-lipoxygenase product 12- hydroperoxyeicosatetraenoic acid, and SS effects were not altered by the 12-lipoxygenase inhibitor baicalein. These data implicate 5- lipoxygenase metabolite(s) (probably leukotriene C4) as a mediator for the IM-augmenting effect of SS. In addition, when the IM effect is blocked by lipoxygenase inhibitors, both SS and AA elicit another outward current that is not blocked by either lipoxygenase or cyclooxygenase inhibitors, suggesting a direct role of AA itself distinct from the IM effect. SS did not alter significantly Ca(2+)- dependent action potentials or, in whole-cell recordings, inward currents likely to represent high-threshold Ca2+ currents. The combined results of these studies suggest that SS hyperpolarizes hippocampal neurons by two mechanisms, both mediated through the AA system. However, one mechanism (IM) involves a metabolite of AA and is most effective at slightly depolarized potentials, whereas the other may involve AA itself and be more effective at membrane potentials near rest.

[basileuz]

It's interesting. Can this compound be obtained otc anywhere?

It's available OTC here in Brazil.

 

 

 

 

The drug did not improve the performance of young animals in the study.

 

Ah.  Not for the young ones among us then...

 

It might still be useful in combination with other nootropics and enhance learning, besides preventing aging in the first place. The behavioral changes are interesting. 

[pleiotropic]

Or it could be detrimental.  We wouldn't know without further research in humans.

 

 

 

 The behavioral changes are interesting. 

 

Hmm... which behavioural changes are you referring to?  The suicidal ideation that the FDA was investigating?

 

http://www.fda.gov/D...s/ucm165489.htm

 

 

 

The reported neuropsychiatric events include postmarket cases of agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide), and tremor.

 

[normalizing]

sounds like side effects i get from just about anything, from simple bean soup to a mg of aspirin and beyond

[basileuz]

Postmarket monitoring is thrash. No placebo group means no completely reliable way to rule out other causes.

No study can prove any serious side effect to montelukast. Also, the postmarket warning is to the general class of this drug, not to the drug itself.

Only way it even exists is for big pharma to avoid getting sued off their asses.

 

I believe there is a significant likelyhood it will enhance learning, but, of course, I have no way whatsoever to prove it.

 

 

 

Or it could be detrimental.  We wouldn't know without further research in humans.

 

 

 

 The behavioral changes are interesting. 

 

Hmm... which behavioural changes are you referring to?  The suicidal ideation that the FDA was investigating?

 

http://www.fda.gov/D...s/ucm165489.htm

 

 

 

The reported neuropsychiatric events include postmarket cases of agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide), and tremor.

 

 

[angus]

I received mine and will start it this week-end. Except feedback from me next week.

[Athenaze]

Does anyone know what the human equivalency dosage would be?  The study used rats or mice, I believe.  How much would a person have to take to mimic these effects, if it is even possible in humans?

 

Thank you.

Edited by Athenaze, 06 November 2015 - 12:41 PM.

[gamesguru]

Twenty-four patients (7 women, 17 men; median age, 55.5 years) with nasal polyps and controlled asthma (n=12 with aspirin intolerance) were treated with 10 mg montelukast once daily for 6 weeks

------------

Sham operated, I/R control and rats treated with montelukast (0.5 mg/kg, po) daily for 7 days then I/R was induced 1 h after the last dose of montelukast. After reperfusion rats were killed by decapitation

 

 

That's 10mg in humans, or 0.5*70/6 = just 5.8mg, scaled from rats [assuming 1:1 ratio of po vs. oral bioavailability]

[BlueCloud]

I've been prescribed montelukast once for my asthma. Never noticed any nootropic or cognitive effects from it.

[angus]

I've been prescribed montelukast once for my asthma. Never noticed any nootropic or cognitive effects from it.

 

at what dosage?

 

I'm testing it since a week, w/ slow ramp up from 10mg to 30mg (won't go more since this is the maximum dosage seen in studies).

at 20 or 30mg a day, I subjectively feel a noots effect, not at 10mg, which is the most common dosage for asthma.

[normalizing]

what does feeling a noots effect even mean?

[gamesguru]

what does feeling a noot's effect even mean?

[basileuz]

what does feeling a noots effect even mean?

 

Well, not sure if that's what he means, but there are some ways I can measure a nootropic's effect, like short-term memory (easilly remembering things like phone-numbers despite only seeing them one time).

 

I've been prescribed montelukast once for my asthma. Never noticed any nootropic or cognitive effects from it.

 

at what dosage?

 

I'm testing it since a week, w/ slow ramp up from 10mg to 30mg (won't go more since this is the maximum dosage seen in studies).

at 20 or 30mg a day, I subjectively feel a noots effect, not at 10mg, which is the most common dosage for asthma.

 

Later this year I will attempt a 20mg dosage.

Can you describe the effects you have obtained?

[normalizing]

gamesguru, why dont you try bluelight forum. its quite an infest of people who think they have a sense of humor

[angus]

>Later this year I will attempt a 20mg dosage.

>Can you describe the effects you have obtained?

 

Sorry, I should have described more than this brief nootropic effect, but I did not have time.

 

I mean, during the 3 days on 20mg or 30mg dosage, my short term memory was better, I had clear ideas and no difficulty to focus.

But I experienced sides effects yesterday on 30mg (3 divided doses): blurred vision. I can't for sure attribute that to montelukast, since I've one confounding factor.

So I'll give it a try again. But it's better to stay at 20mg max for you until I'm sure it's not related to montelukast.

[gamesguru]

gamesguru, why dont you try bluelight forum. its quite an infest of people who think they have a sense of humor

some there have great humor, but i was being serious.  

go about your day normally, don't look for signs of improvement  don't think about a nootropic, you'll psych yourself into thinking it's really working, or that it's screwed you up.  no expectations, no hopes; treat it like breakfast, eat it an forget it, put it behind you.

[BlueCloud]

 

I've been prescribed montelukast once for my asthma. Never noticed any nootropic or cognitive effects from it.

 

at what dosage?

 

I'm testing it since a week, w/ slow ramp up from 10mg to 30mg (won't go more since this is the maximum dosage seen in studies).

at 20 or 30mg a day, I subjectively feel a noots effect, not at 10mg, which is the most common dosage for asthma.

 

 

I don't remember as it was more than a year ago, but  it was for my asthma so I guess it was just the normal prescribed dosage of 10mg once a day.

[BlueCloud]

what does feeling a noots effect even mean?

 

I find that "Nootropic" is a term that has been abused for quite some time on this forum, many people are basically using it as a generic term to describe anything psychoactive..

[Santi]

A study I read about an anti-inflammatory used on the skin of mice took two weeks for the skin to revert to a younger form and two weeks to go back to normal after stopping. The montelukast study says it was a 6 week treatment. Makes sense that to get the desired cognitive benefits you would have to take it daily for a few weeks.

[BlueCloud]

As my asthma has been coming back, I've been prescribed Montelukast again ( 10 mg ) among other things, for three months.

I'll report if I notice any cognitive benefits. Also, I'm an older guy , and so I fit the profile of the older rats that benefited from it 

[cargocultist]

Retailer discussion is here: http://www.longecity...e-modifiers-eu/

[BlueCloud]

One thing that leaves me a bit skeptical, is that Montelukast isn't some obscure drug, it's one of the most used and most popular treatments for one of the most widespread diseases ( asthma ). By now we should have been flooded by thousands and thousands of reports about  people witnessing significant ( and positive) cognitive changes . And yet this is the first time I , and many others , ever heard of such thing by way of this recent study on rats...

[normalizing]

try visiting asthma associated forums for more valid long term reports on this. i dont think this place has many asthmatics using it to report....

[LongLife]

One thing that leaves me a bit skeptical, is that Montelukast isn't some obscure drug, it's one of the most used and most popular treatments for one of the most widespread diseases ( asthma ). By now we should have been flooded by thousands and thousands of reports about  people witnessing significant ( and positive) cognitive changes . And yet this is the first time I , and many others , ever heard of such thing by way of this recent study on rats...

 

BLUECLOUD: Last year I contrived a strong cold due to strange weather events and being in a new location; doctor said I had asthma and underwent 45 minutes of inhalation therapy, blaw, blaw, blaw...all the time thinking about the diagnosis. I became somewhat irritated the more I thought about it. Anyways, I researched asthma a great deal (PUBMED). I do not have asthma, I had a stupid doctor. MEANWHILE, asthma is a catch all word, somewhat as is SCHIZOPHRENIA, for a variety of symptoms, THEREFORE, as many asthma episodes are psychosomatic in nature aggravated by acute stress, etc., etc., my point is that in fact many people may well have, and may have, " witnessed significant (and positive) cognitive changes"  without understanding the significance od the cognitive effect(s), being as they were/are concerned about the episode experience (shortness of breath for instance).

 

I am thinking along this line of thought, a request for forum members to reply to a questionnaire concerning their asthmatic condition and medication. Possible we could get some interesting consensus on members experiences, as well as enlighten them on the subject matter. They would in turn perhaps take their anti inflammatory MONTELUKAST at a non-episode time and report their experience.

 

I just called a friend who has a couple of pharmacies here (PERU) but she is out of town for the New Year's celebrations. I will get some Montelukast, test it out and report back. I will also make contact with purchasers/users, via my friend, and question them and explain why. If in fact this works out in a positive fashion, I will suggest it to a few of my "patients" whom I "advise" who have the symptoms of dementia and run some tests with them also. A few are with Parkinson, a few with Alzheimer's, a few with Mild Cognitive Impairment and a couple with: I have no idea as of yet. The basis will be to test improved short term memory first ("noot effect") without any other nootropic ingestion. Cheers.

[BlueCloud]

 

One thing that leaves me a bit skeptical, is that Montelukast isn't some obscure drug, it's one of the most used and most popular treatments for one of the most widespread diseases ( asthma ). By now we should have been flooded by thousands and thousands of reports about  people witnessing significant ( and positive) cognitive changes . And yet this is the first time I , and many others , ever heard of such thing by way of this recent study on rats...

 

BLUECLOUD: Last year I contrived a strong cold due to strange weather events and being in a new location; doctor said I had asthma and underwent 45 minutes of inhalation therapy, blaw, blaw, blaw...all the time thinking about the diagnosis. I became somewhat irritated the more I thought about it. Anyways, I researched asthma a great deal (PUBMED). I do not have asthma, I had a stupid doctor. MEANWHILE, asthma is a catch all word, somewhat as is SCHIZOPHRENIA, for a variety of symptoms, THEREFORE, as many asthma episodes are psychosomatic in nature aggravated by acute stress, etc., etc., my point is that in fact many people may well have, and may have, " witnessed significant (and positive) cognitive changes"  without understanding the significance od the cognitive effect(s), being as they were/are concerned about the episode experience (shortness of breath for instance).

 

I am thinking along this line of thought, a request for forum members to reply to a questionnaire concerning their asthmatic condition and medication. Possible we could get some interesting consensus on members experiences, as well as enlighten them on the subject matter. They would in turn perhaps take their anti inflammatory MONTELUKAST at a non-episode time and report their experience.

 

I just called a friend who has a couple of pharmacies here (PERU) but she is out of town for the New Year's celebrations. I will get some Montelukast, test it out and report back. I will also make contact with purchasers/users, via my friend, and question them and explain why. If in fact this works out in a positive fashion, I will suggest it to a few of my "patients" whom I "advise" who have the symptoms of dementia and run some tests with them also. A few are with Parkinson, a few with Alzheimer's, a few with Mild Cognitive Impairment and a couple with: I have no idea as of yet. The basis will be to test improved short term memory first ("noot effect") without any other nootropic ingestion. Cheers.

 

 

Your point about Montelukast probably helping  those ( without them knowing it) with psychosomatic asthma is interesting ( if it really has cognitive effects),  but I suspect that the ratio of real asthma ( the ones correctly diagnosed ) to psychosomatic asthma is much higher in the world, although I don't have any numbers to support that. There are also some symptoms that are trademarks of real asthma, like audible wheezing, wich you almost never find in cases of psychosomatic asthma ( often called silent asthma, because of the absence of wheezing ). So I still think that by now, we should have had substantial reports of collateral cognitive enhancement by people correctly diagnosed with non-psychosomatic asthma and taking Montelukast.

 

My old mother is a long-time serious asthma sufferer ( to the point of being hospitalized at times ), and I just found out she was on Montelukast for quite sometime now, but she didn't notice anything special going on cognitive-wise . But then again she is kind of retired and doesn't do much during the day anyway, so perhaps she is not noticing it.

 

I've been myself on Montelukast for more than a month now ( and will be on it for another two months, by prescription of my doctor ), and honestly can't say I've noticed any changes at all on the cognitive side. In fact , I'm not even sure it's doing anything for my asthma either, as I'm also taking an inhaled bronchodilatator combined with a corticosteroid ( Seretide, an inhaled combination of fluticasone and salmeterol )

 

If that upcoming human study with Montelukast shows any improvement at all, I suspect it won't be at the normal dosages usually prescribed for asthma, probably much higher dosages.

[LongLife]

 

what does feeling a noots effect even mean?

 

Well, not sure if that's what he means, but there are some ways I can measure a nootropic's effect, like short-term memory (easilly remembering things like phone-numbers despite only seeing them one time).

 

I've been prescribed montelukast once for my asthma. Never noticed any nootropic or cognitive effects from it.

 

at what dosage?

 

I'm testing it since a week, w/ slow ramp up from 10mg to 30mg (won't go more since this is the maximum dosage seen in studies).

at 20 or 30mg a day, I subjectively feel a noots effect, not at 10mg, which is the most common dosage for asthma.

 

ANGUS: It has been about six weeks now. Can you tell any improvement taking the higher dose of Montelukast ?

 

Later this year I will attempt a 20mg dosage.

Can you describe the effects you have obtained?

 

ETININ: Have you noted any additional effects from 20mg doses of Montelukast yet?