5-HT2B Agonists and the heart

[rickolasnice]

Why bad?

Is it long term?

 

[rickolasnice]

OK sorry for bein lazy.. just went over to wiki to work it out for myself so i now know why bad.. but i still want to know: Is it long term?

Once the drug causing the 5-HT2b agonism is out of your system.. is your heart safe to fight another day with no complications? If you get what i mean

Edit: OK, OK.. i got another question.. how do you know if a chemical will be a 5-HT2b agonist? I remember someone saying 4-MMC is a very likely if not sure fire candidate for being one.. but how do we know?

 

[vortex30]

Well someone I know who I trust quite a bit tells me 4-MMC most likely is NOT a 5HT2b agonist. One thing to note is that a lot of psychedelics and drugs, I guess, are not specific to one 5HT site, rather, they bind to many, but psychedelics for example will MOSTLY bind to 5HT2a, though I think they bind ever so slightly to 5HT2b and all the other sites as well. What you want to look out for is something that has a lot of affinity for 5HT2b agonism and I think one of them is PMA.

That's my knowledge on the subject, anyways.

 

[Sturnam]

I'm pretty sure you only have to worry about long-term administration of the 5-HT2B agonists. That is, because it produces a thickening of cardiac values, repeated adminstration won't immediately shrink the cardiac valves. Because the agonism produces physical growth, it'll persistent even when the stimulus is gone. I think it should go away on its own, assuming you stay away from them. Don't know how long it would take though. Exercise would probably help to get rid of that extra fiber around the valves.

As for how you know things are, SAR's can give you a guess, but to know for sure it's up to sophisticated lab equipment to put 5-HT2B receptors on a plate and see if drug X activates them.

 

[Hammilton]

In short: Yes, 5HT2b agonism is mostly a long term problem. This is why fenfluramine was pull.

Well someone I know who I trust quite a bit tells me 4-MMC most likely is NOT a 5HT2b agonist. One thing to note is that a lot of psychedelics and drugs, I guess, are not specific to one 5HT site, rather, they bind to many, but psychedelics for example will MOSTLY bind to 5HT2a, though I think they bind ever so slightly to 5HT2b and all the other sites as well. What you want to look out for is something that has a lot of affinity for 5HT2b agonism and I think one of them is PMA.

That's my knowledge on the subject, anyways.

Actually, many psychedelics have higher affinity for other 5HT receptors than 2a. My memory is particularly bad here, but I know someone will have an answer. I'm pretty sure that both LSD and DMT have higher affinity for 5HT1a than for 5HT2a. The tryptamines are particularly messy with respect to 5HT receptors.

Are you referring to this?

It isn't too bad at all.


Methamphetamine is fucking toxic, it is an effective dual DA/SE cascader aswell as a slight reuptake inhibitor, Methcathinone and mephedrone are the other way around, they are decent reuptake inhibitors, with less of a cascading effect, particularly on dopamine as the ketone on the beta carbon is electronegative and won't fit through SER correcctly, despite the methyl being partially SE mimicking the cascade is still small, and the reuptake inhibition fairly abysmal for the same reason.
Thus the SE release is far less for both chemicals, meaning that : -

A) The cathinone is not take up into the presynaptic neuron (despite the methyl being a hydroxyl mimicker) where due to the methyl on the amine and alpha carbon, it inhibits MAO to a large degree, creating an MAOI effect.

B) The dual release, and consequent DA "hoover" effect is significantly lessened, again resulting in less breakdown product damage in the neuron.

For the dopamine side of things, the molecules double bonded carbon makes it a far more effective DARI as opposed to releaser, again product breakdown inside the neuron is far less and the overall subsequent monoamine depletion is less, leading to far lower depletion. Again as the molecular is primarily a reuptake inhibitor as opposed to a cascader MAO inhibition is not seen to anywhere near the same degree as amphetamines/methamphetamines, however you do notice a definate adrenaline increase after the drug has worn off, as the DARI action lessens and the amount of DA and consequently NA/A in the presynaptic neuron shoots up causing a cascade.

Evidence to support these claims.

Cathinones cause a fairly hefty DA mediated rise in body temperature, and the high is far more of a sustained one than the initial rush (cascade) of amphetamines. Cascaders are fucking evil in principle, I really can't understand why people have used and DA mimicked for so fucking long .

MBDB is primarily serotonergenic with little to no DA effects, yet as soon as you put a double bonded oxygen on it, you get a much higher affinity for the NE and DA transporters and considerably lessened to almost nill reuptake into the SE neuron.

Dimethylamphetamine is nearly inactive, because the molecule is a shit DARI, and causes it's effects through cascading, whereas Dimethylmethcathinone is only 1.6x less active than methcathinone (with the extra steric bulk on the amine compensating for the lowered charge and bining) proving that the primary mechanism of the cathinones is reuptake inhibition as opposed to cascading.

The above information showing cathinones lesser affinity for the SE transporter also means that compounds such as 4 methoxy amphetamine, and 4 methyl amphetamine are rendered harmless as MAOI's as they do not get transported into the presynaptic SE neuron, hence no massive overheating.

Furthermore, the 4 fluorinated and 4 methylated versions of both methcathinone and cathinone will have barely any 5HT2b agonism, as SE, being a mood regulator amongst other things, will have evolved to not accept electronegative groups there, otherwise NE/E would have a far larger effect, causing heart issues in humans.

It's 100% abso-fucking-lutely pure nonsense. Madge / thereisnomadge / whatever has no fucking clue what he is talking about 90% of the time. There's a reason he doesn't post here anymore- we're not stupid enough to accept the drivel he spews. Don't take any sort of evidence from someone who directly benefits from increased use of the drug.


Take the bold area, for example. He says that the cathinone analogue of para-methoxy-amphetamine is "harmless as [an] MAOI." It's good that he knows that because there's absolutely ZERO evidence for the claim. It doesn't matter if the drug releases serotonin (or other monoamines) as long as it's blocking the reuptake, increased concentrations result. If it is indeed an MAOI- and there's nothing to support the claim that it isn't- it could easily cause hyperthermia, hypertension and death just like poor dosing with an MAOI + MPH would. You can't carefully titrate your doses if you're combining the effects of two drugs into one.

Would you want to be the lucky bastard to who gets to die because you believed his nonsensical reasoning? Anyone who can predict affinity based upon nothing but convoluted logic should not be believed.

Then consider his explanation that it doesn't have 5HT2b affinity. He's based this off of the supposed lack of affinity NE has for 5HT2b receptors (I didn't find anything saying this is true or not), because both NE and the cathinones have an oxygen atom attached to the beta-carbon.

Using that same logic, because NE is not a good DARI, the cathinones shouldn't be either.

H-Bond donors and H-Bond acceptors are not equal, if he wasn't aware.


Basically it comes down to this: Little or nothing is known about mephedrone besides that it's a euphoric stimulant. It's reasonabe to assume that it's a DA and NE reuptake inhibitor, probably with some serotonergic activity as most of the 4-substituted amphetamines have serotonergic activity. However, with regard to it's effect on 5HT2b receptors that don't result in a psychoactive effects, there is no logic that can predict whether 4-methylmethcathinone will have affinity. Regarding the terribly named "methedrone:" only a terrible human being with no concern for who he hurts would sell something so closely related to and likely to be both an MAOI and a monoamine reuptake inhibitor.

 

[vortex30]

I was referring to Madge, indeed. He doesn't have a real mephedrone/RC business anymore, but indeed he is still creating crazy analogues all the time.

 

[Hammilton]

If he told you the earth was round, you'd be well advised to triple check.

Nothing he says has an ounce of validity. I know he said they were getting 'methedrone' in stock, for which I put in the required berating, but anyone who actually sell the stuff is human garbage.

 

[pofacedhoe]

If he told you the earth was round, you'd be well advised to triple check.

Nothing he says has an ounce of validity. I know he said they were getting 'methedrone' in stock, for which I put in the required berating, but anyone who actually sell the stuff is human garbage.

too true.

money and truth do not mix its either one or the other