Methylone & 5-HT2B agonism

[Twigs]

I have seen it mentioned a few times that methylone doesn't act as a 5-HT2b agonist.

Are there any scientific literature that backs this up? I haven't been able to find any.

 

[Solipsis]

Best I can find is this:

Iversen et al. (2013) also reported submicromolar affinity binding of 5- and 6-APB and 5-IAI to h-Alpha2A adrenoceptors, but the significance of this is not clear. Simmler et al. (2013) and Eshleman et al. (2013) tested a series of cathinone derivatives against a range of h5-HT receptors and adrenoceptors but failed to find any potent interactions

Maybe best if read in context here, so that it is suggested that the cathinone derivatives are ones like bk-MDMA:
http://bitnest.ca/external.php?id=%7DbxUgY%5CC%40%1BZ%21%3F%3D%5BE%0F%0A%13_JKw%7Cd%0BUhfGF%7E
(It was after mention of a range of compounds that DO bind potently to 5-HT2b, also found in the article called "Neurochemical profiles of some novel psychoactive substances.")

Oh dammit, no. I don't think they screened 5-HT2B, although indeed methylone was included:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572571/

So, no idea... maybe no affinity for that receptor was found because it was not included in those screens and people assume that it means: no affinity.

 

[sekio]

I'd bet that it still had affinity for 2b...

 

[Solipsis]

The cardiovascular effects of methylone are really prominent. I'd say that if you'd do it frequently not only would you risk chronic fatigue from dopamine depletion / damage but the acute heart and bloodvessel stress seems at least as troublesome as the heart valve / cardiac fibrosis (iirc?) from chronic 5-HT2B agonism.

And yeah I think so, too. Sekio. MDMA itself is a potent agonist, and I might have read about 4-MMC being one as well. Although suprising apparently not all cathinones are risky that way. So it's suspicious at best.

 

[Twigs]

Iversen et al. (2013) screened 14 drugs against a wide range of human monoamine and amino acid receptors in vitro and detected very few submicromolar interactions. The most notable finding was the high affinity binding of mephedrone, 5-APB, 6-APB and 5-IAI for 5-HT2B receptors.

I can't figure out if methylone is among the 14 drugs, but since both MDMA, mephedrone, 6-apb and 5-apb all have affinity to the 5-HT2B, I would find it strange if methylone wouldn't as well.
I have used it far to much since 2007, every weekend for several years, but about once a month the last couple of years. Going for a check up next week to see if any serious damage has been done.

 

[Solipsis]

I can't figure out if methylone is among the 14 drugs, but since both MDMA, mephedrone, 6-apb and 5-apb all have affinity to the 5-HT2B, I would find it strange if methylone wouldn't as well.
I have used it far to much since 2007, every weekend for several years, but about once a month the last couple of years. Going for a check up next week to see if any serious damage has been done.

It's not.

http://bitnest.ca/external.php?id=%7DbxUgY%5CC%40%1BQ.%3A%27UGIYQ%03VWv%7F%7E%15Uo

5-APB, 6-APB, benzedrone, 2-DPMP, MDAI, 4-MEC, 5-IAI, DMAA, MPA, BMDP, naphyrone, 1-naphyrone (obscure as fuck?), MDAT

 

[sekio]

So naphyrone and the APBs are 5ht2a agonists but methylone isn't? I don't habeeb it. I think they just missed testing methylone.

 

[ebola?]

I'd bet that it still had affinity for 2b...

Yeah. . .the BOx series and bk-2cb demonstrate retention of psychedelic activity with a variety of beta-substitutions, so I wouldn't be surprised if beta-ketonation didn't abolish MDMA's activity at 5ht2b.

ebola

 

[chaos_destroy]

I would be very shocked if methylone did not act on 5-ht2b given the similarity to MDMA in action and the absolute requirement of 5-ht2b action for MDMA. The likely hood that two chemicals as structurally similar as methylone and MDMA that give such similar effects would work in two completely different ways if highly unlikely.

 

[Black]

I would be very shocked if methylone did not act on 5-ht2b given the similarity to MDMA in action and the absolute requirement of 5-ht2b action for MDMA. The likely hood that two chemicals as structurally similar as methylone and MDMA that give such similar effects would work in two completely different ways if highly unlikely.

exactly. as much as i would appreciate the discovery of a new mechanism for pleasurable mdma-like serotonin release, i'd eat my hat of methylone isn't an agonist at 5-ht2b.

 

[The King of Beans]

exactly. as much as i would appreciate the discovery of a new mechanism for pleasurable mdma-like serotonin release, i'd eat my hat of methylone isn't an agonist at 5-ht2b.

Could be, but from what I recently read (From Captain Kratom, who posted links to proven studies) the APB's are FAR MORE of an antagonist than MDMA. And I bet Methylone is probably about the same as MDMA. So that means. MDMA and Methylone are not all that dangerous for your heart? I abused MDMA for nearly 20 years (on and off) but during my times of doing it, I do it almost everyday. And I am still here. So I know MDMA isn't that bad for your heart (but I bet you my left testicle it DOES cause some damage. No drugs are good for you, period. Unless they are natural/organic like marijuana....but even marijuana can cause some serious problems. But I bet if you had organically grown with no chemicals, it wouldn't be so bad)

 

[《Plasticity》]

^ I fail to see how the APB's affinity for 5-ht2b is relevant to how strong an agonist methylone is. Are you saying that because methylone is an MDMA analogue that it's bound to have the same or a similar side-effect profile? Because the APB's are MDA analogues after all, and fenfluramine as well as aminorex are both methamphetamine analogues iirc.. Dude, you say "your still here" like no damage has been done but you made a thread in detail deacribing all sorts of health issues from these drugs, symptoms that sound in line with heart disease. Valvular heart disease is progressive and doesn't always immediately lead to an acute heart attack, typically it's a slow painful death from heart failure if left untreated. Now I'm starting to think your in denial

 

[Student76]

Hello.

As I tested Methylone about 10 times I think its very cardiotoxic.I took 8 times molly and never had these heart problems.
The euphoria was nice for 2 hours,then faded.But I felt the next day a stabbing pain in the chest.Each time i used it.Tho it think its dangerous.
Perhaps its the moleküle part which is from MDMA.

Because now I use 3 years 3 MMC,never felt pain near the heart,high pulse or high blood pressure.Conclusion there mußt be a difference.
With methylone I had severe pain in the chest after only 150 mg.

My few words.

I would be nice to see if the APBs are stronger or weaker on 5 ht2b than methylone or molly.

Anja Stockholm

 

[ebola?]

The APBs are stronger full agonists (some research indicates that MDA and MDMA are partial agonists at 5ht2b). This is only really an issue with chronic use, and this class of compounds absolutely cannot be dosed frequently (while maintaining positive outcomes).

ebola

 

[TrailBlazzer]

The APBs are stronger full agonists (some research indicates that MDA and MDMA are partial agonists at 5ht2b). This is only really an issue with chronic use, and this class of compounds absolutely cannot be dosed frequently (while maintaining positive outcomes).

ebola

Would mdpv analogues like a-pvp, mdppp, or a-phpp fall into this category? I always hear them referenced to as substituted cathinones but I'm tottally clueless when it comes to advanced chemistry. I've dabbled in these although infrequently but am a little concerned....

 

[ebola?]

Unknown but unlikely. I know that this series tends to have little affinity at SERT (this is at least the case with mdpv). I would be surprised if if any of these compounds had appreciable direct serotonergic agonism.

ebola

 

[nickfurry]

I joined just to find out more about this. I'm bumping this thread because the 5HT2b agonism discussion in the 5-MAPB thread drowns in the other stuff.

Please somebody who is more knowlegable in these things, explain. If MDMA is reasonably suspected to cause heart valve hypertrophy even in casual users, how could anybody say that using 6-APB occasionally might still be safe? The affinity of 6-APB for 5HT2b is more than a 100 times stronger than MDMA, and it has a longer half life as well, not to mention that it seems that people tend to redose more than with MDMA.

When they say that the APB's and 5-IAI are full agonists, is that fact or hypothesis? Wouldn't you have to have the entire intercellular mechanism related to the receptor mapped and understood first? Do we have such complete knowledge of 5HT2b?

Please, somebody, find a silver lining here. A less neurotoxic version of MDMA should not be too good to be true.

Oh and the idea of hundreds of thousands of young people dying of heart disease in the coming years isn't such a bright thought either.

 

[sekio]

If MDMA is reasonably suspected to cause heart valve hypertrophy even in casual users

Where'd you hear that? Certainly heavy or regular use predisposes one to cardiac valvular issues, but I wouldn't go so far to say that casual (1-2x a year) usage causes it for certain.

When they say that the APB's and 5-IAI are full agonists, is that fact or hypothesis? Wouldn't you have to have the entire intercellular mechanism related to the receptor mapped and understood first?

As far as I can tell it's published fact. GPCRs like 5ht2bR are rather well understood, doing things like measuring the downstream activation of cAMP cyclase or whatever is done regularly.

A less neurotoxic version of MDMA should not be too good to be true.

Is responsible use of MDMA that recklessly toxic anyway?

 

[Black]

A less neurotoxic version of MDMA should not be too good to be true.

try mdma for that. with the recent research into proper interspecies dosage scaling with mdma, neurotoxicity at least is pushed into dosages of 700mg+. combine that with the absence of anything other than sert labeling (which can easily be explained by downregulation, which is consistent with the numbers recovering after days/weeks and also consistent with other markers being positive for real serotonergic neurotoxins such as p-I-amphetamine/5,6-dihydroxy-typtamine) giving positive results and the fact that specific death of serotonergic neurons doesn't even occur in huge doses (at around 30mg/kg; there's also death of non-serotonergic neurons at such doses, possibly due to hyperthermia?) and there isn't really much credibility left in the claim that mdma is a neurotoxin with average human use.

some papers to back that up.

 

[nickfurry]

Ok, that sounds somewhat comforting.

But I'm still curious about the very potent 5HT2b agonism of 6-APB etc. Isn't it quite likely that a lot of so called MDMA being sold these days is really a mix of benzofurans?

Several posts on this board and others say 'don't worry, doing 6-APB a few times a year isn't going to get you valvular hypertrophy'.

How is that? It is a very strong full agonist with a somewhat longish half life. Sound like a disaster hiding in the shadows to me.