Dmso Is Similar To Reserpine, Lowers Serotonin, Increases MAO-A

[haidut]

I have suspected that DMSO has central effects given how powerfully sedating it can be for some people. This older study compares the effects of DMSO to the ancient tranquilizer reserpine, which Peat has written about before. This would make DMSO an effective serotonin lowering agent, an anti-depressant, an anti-psychotic medicine, and also potentially libido enhancing. As you can see, in a eerily similar tone to Peat's article on reserpine, DMSO was used successfully as an anti-psychotic drug. Finally, this would make DMSO a good combination with methylene blue not only due to enhancing the absorption of methylene blue but also due to the ability of DMSO to reverse the MAO-A inhibition caused bu methylene blue.
Serotonin, depression, and aggression - The problem of brain energy.
"...Reserpine is an ancient tranquilizer, derived from a plant used in India for centuries. It has a powerful tranquilizing action, has been used to treat hypertension, and was found to be an antidepressant (Davies and Shepherd, 1955). It lowers the concentration of serotonin in the brain and other tissues. Isoniazid, an antidepressant that came into use in the 1950s, is effective, but it probably has no effect on serotonin. When those drugs were popular, serotonin wasn’t recognized as a “neurotransmitter.” It wasn’t until the 1960s that our present set of doctrines regarding serotonin’s effects on mood and behavior came into being."

EFFECTS OF DIMETHYL SULFOXIDE AND ALPHAGLUCOCHLORALOSE ON PENTYLENETETRAZOL CONVULSIVE THRESHOLDS IN MICE - Braude - 2006 - Annals of the New York Academy of Sciences - Wiley Online Library
"...The mechanism of action of DMSO and AGC on PTZ seizure thresholds is yet unknown, but from the emerging facts, an hypothesis may be formulated. The effects of DMSO in this test are remarkably similar to those of a 10 mg/ kg of reserpine as described by Bastian.' Reserpine also decreased the threshold to persistent tonic seizures, did not block hindleg extension and shortened time to death. In addition to this similar action on PTZ seizure thresholds, DMSO has exhibited some of the pharmacological profile of reserpine. Like this compound, it increases hexobarbital sleeping time of mice,' lowers body temperature and decreases spontaneous motor activity of mice. In man, Ramirez and Luzag have also reported that DMSO, given i.m. to 42 severely disturbed psychotic patients, produced emotional calm and relieved some psychotic and psychoneurotic symptoms. When AGC is given with a dose of 5 gm/kg of DMSO, the effect of DMSO on the PTZ tonic seizure threshold is reversed, although DMSO somewhat prevents the full anticonvulsive activity of AGC. Because Bonnycastle" has reported significant increases in rat brain serotonin levels after intraperitoneal administration of chloralose and chloral hydrate, the reversing of the DMSO effect by AGC might be comparable to the reversing of the reserpine effect by monoamine oxidase inhibitors."

 

[charlie]

Incredible. Great stuff haidut!

 

[Koveras]

Wasn't one of the properties of reserpine that it decreased dopamine (as well as serotonin)? Hence the tranquilizing effects. Still mostly accurate for the ideas you presented, except maybe libido-enhancing.

I saw recently you also made this comment in another thread:

Why do you think DMSO is helpful at all for hairloss?? The only reason I can see for combining it with MB is to increase absorption. But absorption is already pretty good even without DMSO, and actually MB can cause oxidative damage if local concentrations become too high.

If that were the case maybe better to use separate routes of administration?

 

[Elephanto]

I don't think raising Mao-a is something desirable.

MAO-A-induced mitogenic signaling is mediated by reactive oxygen species, MMP-2, and the sphingolipid pathway
MAO-A-induced mitogenic signaling is mediated by reactive oxygen species, MMP-2, and the sphingolipid pathway. - PubMed - NCBI

High expression of mao-a in prostate cancer
Targeting monoamine oxidase A in advanced prostate cancer. - PubMed - NCBI

Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis.
Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis. - PubMed - NCBI

"MAOA-dependent HIF1α/VEGF-A/FOXO1/TWIST1 pathway"

 

[haidut]

I don't think raising Mao-a is something desirable.

MAO-A-induced mitogenic signaling is mediated by reactive oxygen species, MMP-2, and the sphingolipid pathway
MAO-A-induced mitogenic signaling is mediated by reactive oxygen species, MMP-2, and the sphingolipid pathway. - PubMed - NCBI

High expression of mao-a in prostate cancer
Targeting monoamine oxidase A in advanced prostate cancer. - PubMed - NCBI

Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis.
Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis. - PubMed - NCBI

"MAOA-dependent HIF1α/VEGF-A/FOXO1/TWIST1 pathway"

I guess it depends on the context. MAO-A is inhibited by radiation, surgery, trauma, etc. So, if it is already inhibited I think restoring its normal function can be beneficial. Reserpine does boost MAO-A and it is one of the oldest drugs in existence. If it was causing or promoting cancer it would have shown up by now.

 

[tara]

'Reserpine also decreased the threshold to persistent tonic seizures'

Just checking what you understand my this. Does decreasing the threshold for seizures mean making the seizures more likely/frequent?

'lowers body temperature'

This is a good thing? A number of us are trying to raise our temps?

 

[Elephanto]

If it was causing or promoting cancer it would have shown up by now.

That's a precipitous conclusion. Reading those studies show that Mao-a would do this by promoting angiogenesis (VEGF / HIF-1) just like nitric oxide does. People don't get cancer from smoking cigarettes for 10 years, or by eating garlic daily which also promotes nitric oxide or tons of other stuff that increase angiogenesis. It's still a slow process that takes 50+ years before you get cancer, so I don't think that it would be necessarily known that Reserpine promote cancer.

Maybe mao-a inhibition is actually part of what makes Methylene blue an anti-cancer/pro-longevity agent; and those studies I linked kind of confirm that.

 

[treelady]

Just checking what you understand my this. Does decreasing the threshold for seizures mean making the seizures more likely/frequent?

Decreasing(lowering) the threshold for seizures means making seizures more likely - not a good thing.

Also "Reserpine also decreased the threshold to persistent tonic seizures, did not block hindleg extension and shortened time to death." Hmmm... I'm not good at reading studies, but I would interpret that to mean it makes seizures more likely and death to result faster. I usually muscle test "no" on DMSO but last night I got an "ok" so tried DMSO on my back for horrible back pain. Smelled awful but seemed to help some however, I am going to be very careful with it since "DMSO has exhibited some of the pharmacological profile of reserpine" and I have epilepsy.

 

[tara]

Decreasing(lowering) the threshold for seizures means making seizures more likely - not a good thing.

Also "Reserpine also decreased the threshold to persistent tonic seizures, did not block hindleg extension and shortened time to death." Hmmm... I'm not good at reading studies, but I would interpret that to mean it makes seizures more likely and death to result faster.

That's how I read it too.

 

[thyrulian]

Decreasing(lowering) the threshold for seizures means making seizures more likely - not a good thing.

Also "Reserpine also decreased the threshold to persistent tonic seizures, did not block hindleg extension and shortened time to death." Hmmm... I'm not good at reading studies, but I would interpret that to mean it makes seizures more likely and death to result faster. I usually muscle test "no" on DMSO but last night I got an "ok" so tried DMSO on my back for horrible back pain. Smelled awful but seemed to help some however, I am going to be very careful with it since "DMSO has exhibited some of the pharmacological profile of reserpine" and I have epilepsy.

I doubt increasing MAO-A has anything to do with reserpine's propensity for lowering the seizure threshold.

After all, don't histamine, norepinephrine & serotonin (through glutamate) all enhance cellular excitability?

 

[thirdcatgy]

Haidut ~ The challenge with DMSO is that it can be a potent mast cell destabilizer and has been show to even cause anaphylaxis in sensitive individuals {likely sulfa pathways ,etc.}. It would be great if you could offer and DMSO-free alternative to the products which do contain it. I would think many (including myself) are interested in keeping MCs in check due to higher estrogen levels, etc.

You've mentioned previously that even aspirin and water is absorbed up to 80% in the first hour of application ~ I would happily forgo any increased absorption rate that the DMSO might lend to keep the aforementioned in check.

 

[haidut]

Just checking what you understand my this. Does decreasing the threshold for seizures mean making the seizures more likely/frequent?


This is a good thing? A number of us are trying to raise our temps?

I guess the effect on seizure threshold would not be good. The lowering of temperature would depend on context. Serotonin can raise temps and cause fever but in a bad way. GABA drugs usually lower temperature and they are very therapeutic.

 

[haidut]

That's a precipitous conclusion. Reading those studies show that Mao-a would do this by promoting angiogenesis (VEGF / HIF-1) just like nitric oxide does. People don't get cancer from smoking cigarettes for 10 years, or by eating garlic daily which also promotes nitric oxide or tons of other stuff that increase angiogenesis. It's still a slow process that takes 50+ years before you get cancer, so I don't think that it would be necessarily known that Reserpine promote cancer.

Maybe mao-a inhibition is actually part of what makes Methylene blue an anti-cancer/pro-longevity agent; and those studies I linked kind of confirm that.

All I am saying is that a number of toxic insults inhibit MAO-A and restoring it to normal seems to be beneficial. The goal of this post was to point the similarities between DMSO and reserpine, not pick on specific effects. Btw, aspirin also lowers seizure threshold. Is that a reason to avoid it?

 

[haidut]

Haidut ~ The challenge with DMSO is that it can be a potent mast cell destabilizer and has been show to even cause anaphylaxis in sensitive individuals {likely sulfa pathways ,etc.}. It would be great if you could offer and DMSO-free alternative to the products which do contain it. I would think many (including myself) are interested in keeping MCs in check due to higher estrogen levels, etc.

You've mentioned previously that even aspirin and water is absorbed up to 80% in the first hour of application ~ I would happily forgo any increased absorption rate that the DMSO might lend to keep the aforementioned in check.

Noted. I may actually do that for all products except the steroid ones since for steroid absorption and effect potentiation DMSO is key. Keep in mind that the amount of DMSO in my supplements are a tiny raction of a percent compared to the ones used in these studies. If you take a full dose of any of my DMSO supplements you are getting no more than 700mg DMSO and most studies used tens of grams per day to observe these effects. I think the concerns about DMSO are well-intentioned but unjustified considering the history of use and exposure form the doses in things like dietary supplements. The current data states that systemic toxicity from DMSO is VERY LOW, even at tens of grams per day. Not to say that people should not be careful with what they ingest but we need to be fair to all ingredients used. I can post studies showing aspirin, taurine, riboflavin, etc have higher toxicity than DMSO if taken in higher enough doses, which some people oon the forum easily reach with supplementation.

 

[thyrulian]

All I am saying is that a number of toxic insults inhibit MAO-A and restoring it to normal seems to be beneficial. The goal of this post was to point the similarities between DMSO and reserpine, not pick on specific effects. Btw, aspirin also lowers seizure threshold. Is that a reason to avoid it?

Hey, might that have anything to do with the acetyl group?
I felt great on aspirin starting out, but worse after a couple days.

 

[haidut]

Hey, might that have anything to do with the acetyl group?
I felt great on aspirin starting out, but worse after a couple days.

I think the official explanation was its uncoupling effect, so things like DNP and very high doses of thyroid would also have it. Also, high dose aspirin depletes glycine in the organism as glycine conjugation to form hippuric acid is the main pathways for excreting aspirin. And given that glycine is the major inhibitory neurotransmitter in the CNS, lower levels can lead to seizures.

 

[tara]

Btw, aspirin also lowers seizure threshold. Is that a reason to avoid it?

Not a good reason for everyone to avoid it. But if seizures are one's major problem, and aspirin was likely to increase their frequency, then it might be very relevant.

 

[tara]

Not to say that people should not be careful with what they ingest but we need to be fair to all ingredients used. I can post studies showing aspirin, taurine, riboflavin, etc have higher toxicity than DMSO if taken in higher enough doses, which some people oon the forum easily reach with supplementation.

I don't think DMSO is the only thing to consider the safety of.
I think it would probably be a good thing if people were aware of the risks with these other substances too.
I am from time to time alarmed by the extreme doses people are taking or considering of some potentially hazardous substances, that I would consider riskier than the DMSO in your supplements for most people.
But no particular forum member is obliged to do the work on all substances to provide complete comprehensive balance. This is a voluntary enterprise, and people get to pursue the areas they are interested in. I appreciate you posting the information you do here. As you know, I tend to post a few cautions about other substances and strategies too, including excess caffeine, thyroid, potassium, calcium + baking soda, and starvation.

I take some things that I am aware have some risk attached (currently eg fever few, high-dose riboflavin), because there is also evidence of them being at least sometimes helpful to people with my issues, and I think the risk may be worth it to find out. Esp. given that I'm sure there are negative effects from the pharmaceuticals I use in the absence of a more effective safe solution so far. I figure the more I know about the downsides as well as the potential benefits, the better risk-benefit analysis I'm likely to make. (though I have other things to do in my life, so I don't intend to research everything comprehensively this week:)) At this point in time, I'm choosing to continue the tyromax by diluting it in water and drinking it, and holding off on the topical DMSO, because I am being cautious of the locally high concentrations. That''s today. My assessments and decisions on lots of things may may change.

I think the concerns about DMSO are well-intentioned but unjustified considering the history of use and exposure form the doses in things like dietary supplements.

Lots of people here are suspicious of many of the other ingredients routinely used in dietary supplements, so while you may be right about the relatively low risk associated with very low systemic concentrations of DMSO, this argument about it having been widely used in supplements for a long time don't strike me as carrying a lot of weight.

 

[Parsifal]

I don't think DMSO is the only thing to consider the safety of.
I think it would probably be a good thing if people were aware of the risks with these other substances too.
I am from time to time alarmed by the extreme doses people are taking or considering of some potentially hazardous substances, that I would consider riskier than the DMSO in your supplements for most people.
But no particular forum member is obliged to do the work on all substances to provide complete comprehensive balance. This is a voluntary enterprise, and people get to pursue the areas they are interested in. I appreciate you posting the information you do here. As you know, I tend to post a few cautions about other substances and strategies too, including excess caffeine, thyroid, potassium, calcium + baking soda, and starvation.

I take some things that I am aware have some risk attached (currently eg fever few, high-dose riboflavin), because there is also evidence of them being at least sometimes helpful to people with my issues, and I think the risk may be worth it to find out. Esp. given that I'm sure there are negative effects from the pharmaceuticals I use in the absence of a more effective safe solution so far. I figure the more I know about the downsides as well as the potential benefits, the better risk-benefit analysis I'm likely to make. (though I have other things to do in my life, so I don't intend to research everything comprehensively this week:)) At this point in time, I'm choosing to continue the tyromax by diluting it in water and drinking it, and holding off on the topical DMSO, because I am being cautious of the locally high concentrations. That''s today. My assessments and decisions on lots of things may may change.


Lots of people here are suspicious of many of the other ingredients routinely used in dietary supplements, so while you may be right about the relatively low risk associated with very low systemic concentrations of DMSO, this argument about it having been widely used in supplements for a long time don't strike me as carrying a lot of weight.

What are the risks with calcium, high caffeine and baking soda?

 

[FredSonoma]

Does anyone know the mechanism by which DMSO lowers serotonin? I find Tyromax seems to make me slightly more bloated, which I wouldn't expect a thyroid supplement to do. However, cypro also makes me a lot more bloated, I think because I unfortunately need my high serotonin to be constantly flushing bacteria from my gut.