5-ht2b full agonist question

[tripz_two]

One apology before I ask my question:
I haven't been on bluelight in forever so I'm sure the answer to this could be found buried in another thread that I haven't seen. However I did a search and found a thread in another forum but they only had 1 or 2 knowledgeable contributors, so I thought I'd restate it here in the hopes of getting a more complete answer.

Basically my main question is that given 5-MAPBs full agonism and low affinity/Ki for the 5-ht2b receptors, I'm wondering from a harm reduction standpoint if dosing 3 times a year @ ~ 120mg each occurrence would be "safe'ish" to prevent heart valve issues? In the other thread the main contributor was stating it should be safe every other month, but I believe went on to say he had only been using for a year - a couple times each month and was blaming a new murmor/regurgitation on his 5-MAPB usage that year. That doesnt seem like extreme usage. So going form a couple times a month to saying once every other month is safe, seems alarming.

I understand no one knows for sure, but some of you guys are the closest to subject matter experts as it gets. Do valve irregularities only occur with chronic use even in substances with very low Ki values?

Also, what is the Ki value for 5-MAPB? Would it be in the same range as 5/6 APB of around 10nm? That value is so low that it bothers me a lot, but I know that total dosage, and halflife play into the equation as well.

Thank!!

 

[dopamimetic]

This interests me too.

Afaik only a small (but relevant and tragic of course) percentage of the aminorex users, back then when it was used as an anorectic, have developed heart valve problems. Does this mean that there are genetic factors too?

Is there the possibility to have a doctor check the heart periodically and to watch out for changes, or is it too late when one sees first signs?
Scary is that for some the worsening progressed even after stopping aminorex usage.. do not know exactly how true this is.

4,4-dimethylaminorex was an outstanding experience for me, possibly the best drug I have ever tried. I have used it for around a month daily (25mg/d), with some tolerance developing and effects fading a bit, but it would be a great aid nevertheless if just these heart issues would not be. I did not feel any signs like chest pain, shortness of breath, vasoconstriction etc. like on some "regular" stimulants, but I guess this has nothing to say but to lead into false feeling of security...?

 

[psychlo0015]

i too am interested in the heart valve issues. to the best of my knowledge 5ht 2b and 2a are found throughout the cardiovascular system. when taking a drug that stimulates all the 5ht 2b in the body its not only effecting the nervousystem but the cardiovascular system in ways you cant really feel. similar to medicinal drugs that are used to combat ilness. you cant always feel the medication working but it's doing something.

the only way around this problem that ive thought up is a medication that antagonizes 5ht 2b / 2a which cannot easily pass the blood brain barrier. its probably possible but just hasnt been developed yet. one possible solution is to take something like sarpogrelate however i havent discovered any information about its ability to cross the blood brain barrier.

by not being able to cross blood brain barrier it would not effect the receptors in the brain leaving them open to stimulation by 5ht 2b agonists while receptors in the cardiovascular system would be blocked.

this is just an idea i have no idea if it would work but its worth a shot imo

 

[endotropic]

This interests me too.

Afaik only a small (but relevant and tragic of course) percentage of the aminorex users, back then when it was used as an anorectic, have developed heart valve problems. Does this mean that there are genetic factors too?

Is there the possibility to have a doctor check the heart periodically and to watch out for changes, or is it too late when one sees first signs?
Scary is that for some the worsening progressed even after stopping aminorex usage.. do not know exactly how true this is.

The 5-HT2B mediated cardicac problems happened with the fen/phen diet drug combo (fenfluramine with phentermine). Specifically the 5-HT2B agonist activity of daily fenfluramine use caused fibrotic overgrowth of valvular tissue leading to mitral valve regurgitation and loss of cardiac output. Basically the heart valves stiffen so they don't close properly and blood flows backwards through the system instead of pumping forward. Aminorex was never shown to cause those types of valvular issues as far as I know (pulmonary hypertension through some other mechanism though).

As far as screening for 5-HT2B induced cardiac damage a doctor just needs to listen to your heartbeat with a stethoscope. They will listen for a faint "gurgling" sound following each heart beat, indicating backflow of blood into the heart through the faulty valves. Once the "gurgle" starts the damage can't be reversed as far as I know, barring surgery. It might be possible to detect the fibrotic tissue (CT scan maybe?) before it builds up to the point the valve malfunctions, but I've never heard of anyone doing that.

The fen/phen cases happened with people using the drug daily for extended periods, I don't think anyone can tell you a usage rate that will keep you 100% safe though.

 

[Pfafffed]

i too am interested in the heart valve issues. to the best of my knowledge 5ht 2b and 2a are found throughout the cardiovascular system. when taking a drug that stimulates all the 5ht 2b in the body its not only effecting the nervousystem but the cardiovascular system in ways you cant really feel. similar to medicinal drugs that are used to combat ilness. you cant always feel the medication working but it's doing something.

the only way around this problem that ive thought up is a medication that antagonizes 5ht 2b / 2a which cannot easily pass the blood brain barrier. its probably possible but just hasnt been developed yet. one possible solution is to take something like sarpogrelate however i havent discovered any information about its ability to cross the blood brain barrier.

by not being able to cross blood brain barrier it would not effect the receptors in the brain leaving them open to stimulation by 5ht 2b agonists while receptors in the cardiovascular system would be blocked.

this is just an idea i have no idea if it would work but its worth a shot imo

Yeah, I wonder if RS-127445 crosses the blood brain barrier, or even if that really matters much.
Check out: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566110/

More discussion on this thread: http://www.bluelight.org/vb/threads...lve-pulmonary-damage-in-combination-with-amps

 

[Cotcha Yankinov]

New study from France suggested that 5-HT2B antagonists could be a therapeutic avenue for MDMA users (and in a different study I think suggested as a therapeutic avenue for the cardiac fibrosis) One explanation for why it might have continued to get worse is that those fibroblasts that proliferate if you stimulate 5-HT2B continue to make collagen after you stop using, but its also inflammatory related and once inflammatory processes kick off they can be hard to stop.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179857/ - Says "The risk factors for HVD are similar to traditional clinical risk factors for atherosclerosis and coronary artery disease and include age, male gender, hypertension, diabetes, triglycerides, and smoking. In fact, the similarities between the two have led to the hypothesis that acquired HVD is primarily a manifestation of atherosclerosis. The hallmark of HVD pathogenesis is the formation of lesions containing cell types that are characteristic of chronic inflammation. These include macrophages, T lymphocytes, and mast cells. Additionally, there are lipoproteins [LDL and Lp(a)] found in human diseased valve lesions, and accumulation of these lipoproteins is mediated, in part, by ECM proteoglycans. Besides lipoproteins, recent evidence has shown that the renin-angiotensin system, particularly angiotensin converting enzyme and angiotensin II, may play a role in HVD pathogenesis. Angiotensin II has a number of potential lesion-forming effects, including inflammation and macrophage and cholesterol accumulation. Therefore, there are multiple mechanisms that initiate HVD and further perpetuate the disease in otherwise normally functioning valve."
Under chapter "1.3 5-HT2 receptors" It talks a little about the similarity between 5-HT2A and 2B and that they probably both play a role in the heart disease, so it makes sense to find a drug that antagonizes both. This study at the very bottom mentions some therapeutic options as well.

Inflammation can be a positive feedback loop; once it gets started its hard to stop it. It might be some environmental insult that kicks off somebodies autoimmune/inflammatory disease but once it gets going even if the insult that caused it is removed the inflammatory process keeps on chugging for a while. There is some evidence that the heart disease can heal to a degree though.
http://www.ncbi.nlm.nih.gov/pubmed/18321937/ -- A study showing 5-HT2A/2B antagonists do help with the fibrosis. 5-HT2A antagonists also make FABULOUS sleep drugs but not many have made it to market(but can be purchased as chemicals) that are very specific for 5-HT2A, besides the already mentioned Sarpogrelate and possibly some inverse agonists at 5-HT2A that are going to be hard to get a hold of, like Pimavanserin.
https://www.ncbi.nlm.nih.gov/pubmed/12732383?dopt=Abstract -- Titled "[h=1]Sarpogrelate HCl, a selective 5-HT2A antagonist, retards the progression of atherosclerosis through a novel mechanism."[/h]So Sarpogrelate is an interesting option.

http://www.ncbi.nlm.nih.gov/pubmed/17950805
Fairly common in MDMA users though. There are other factors that feed into developing this sort of heart disease though, I don't know if somebody who is interested in RCS vs. somebody who is abusing ecstasy are in the same categories of risk.

TL;DR Most of the cardiac fibrosis was found with MDMA/MDA and the diet drugs (both used on a very regular basis). Not everybody got it so there might be a genetic predisposition relating to collagen/fibroblasts or how many serotonin receptors you have on the heart IMO. I wouldn't worry about once a month except what you'll be like when you get older but if you're in more of the risk factor groups for heart disease then worry more. But if concerned I wouldn't supplement with serotonin like nuts over the years because peripheral serotonin matters too, not just 5-HT2B specific drugs. I recall an african tribe got VHD from eating bananas with too much tryptophan. Hope this mess of text was insightful or something lol