• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio

dosages of agomelatine to block the adverse effects of psychedelics on heart valves.

T

T9358

Bluelighter
Joined
Dec 5, 2012
Messages
92
Location
through the wormhole
Correct me if I am wrong please, but agomelantine is a 5-ht2b antagonist,

Would there be any level of HARM REDUCTION when taking psychedelics or for that matter any promiscuous 5-ht agonist, for melatonin.

at any dosage?


*****(I initially posted the compound in question as melatonin but it is -(agomelantine)****
 
Last edited:
Even if that would work, and at reasonable dosages, I think you'd be looking at taking metalonin like every 1 or 2 hours. I'll have a look to see if there are any binding or efficacy values are known, but it might depend on what you are trying block.
Which psychedelics with serious 5-HT2B agonism do you take frequently?
 
Combining a serotonin releaser like MDMA with a 5-HT2B antagonist will block the serotonin release caused by MDMA, and prevent recreational effects - probably, I don't know if anyone's actually tested that. In theory you want a 5-HT2B antagonist that won't cross the blood brain barrier to prevent that interaction.

For a psychedelic with 5-HT2A agonism as the primary MOA the 5-HT2B antagonist shouldn't block the effects, but most people don't use those drugs with enough frequency to worry about valvulopathies.
 
Even weekly is probably not a worry. The fen-phen fuckup was from daily dosing, I thought. Or stuff like methylaminorex where the half life is a million years.
 
If daily dosing over several years can lead to fatal cardiac disease, weekly use could potentially cause behaviorally relevant damage.

Or stuff like methylaminorex where the half life is a million years.
Click to expand...

Since 4mar was never in clinical use or that common on 'the street', it's unclear how cardiotoxic it is.

ebola
 
If anything at all I was thinking, heavy MDMA users, would this not be a possible aid pre/during or even just post roll, to not only get the anti-oxidant potential but the blockade at 5-ht2b.

I had no idea ( referring to a few post above) that any 5-ht release was mediated via 5-ht2b.

Seriously though would a 5-ht2b antagonist kill a roll so bad like as in stop it dead, or dull a certain aspect due to drowsiness.

I know this may sound dumb but how crucial is 5-ht-2b agonism in the periphery CNS to MDMA's 5-ht release or 5-ht receptor agonism, wich then leads me to think --

-- tramadol's 5-ht release would be as bad as or similar to fenfluramine due to daily chronic administration ( sekio has already answered this question for me) and was saying that

if I remember correctly tramadol does not have affinity for 5-ht2b and its 5-ht release does not effect or reach those receptors????

Dapoxetine a selective fast acting SRI feels totally different than tramadol a supposed but disputed SRA( was checking out a dapoxeine/ethylphenidate combo to see effects), and

although subjective to personal body chemistry, : dapoxetine feels and its side effects are far away from tramadols, although I do know tramadol is a slut as far as selective

receptor binding.

I know that was off topic but melatonin did not defer any effects from 5-apb or tramadol ( again subjective)

Any input would be greatly appreciared
 
T9358 said:
If anything at all I was thinking, heavy MDMA users, would this not be a possible aid pre/during or even just post roll, to not only get the anti-oxidant potential but the blockade at 5-ht2b.

I had no idea ( referring to a few post above) that any 5-ht release was mediated via 5-ht2b.
Click to expand...

Take a look at this thread (starting around post #22): http://www.bluelight.org/vb/threads...has-a-poor-affinity-for-SERT?highlight=5-ht2b

Also where did you find that melatonin was a 5-HT2B antagonist? Simple search doesn't turn up anything on pubmed, and nothing on google besides this thread.

T9358 said:
-- tramadol's 5-ht release would be as bad as or similar to fenfluramine due to daily chronic administration ( sekio has already answered this question for me) and was saying that

if I remember correctly tramadol does not have affinity for 5-ht2b and its 5-ht release does not effect or reach those receptors????
Click to expand...

For some bizarre reason serotonin acting on 5-HT2B doesn't seem to cause any cardiac problems. SSRI's have been in use long enough that we can be pretty sure that reuptake inhibitors are safe in that respect.
 
ENDOTROPIC- thank you I am so sorry I got melatonin mixed up with AGOMELANTINE, I was doing some reading and research on some clinical studies, MOD's if there is a way

to edit the title and switch melatonin to agomelantine, that is the compound in question

And endotropic thank you for the call out, its been a long few weeks, so again my bad.

I was just thinking of a way for frequent users of promiscuous 5-ht agonists to not have reduced problems with heart valves ( hypertrophy) via 5-ht2b agonism with a co-

administered compound. and thanks for the link!
 
Done. You can edit your original post to reflect the change as well if you want.

Here's a reference for Agomelatine's 5-HT2B affinity: http://www.ncbi.nlm.nih.gov/pubmed/12750432

If someone can find a reference correlating oral dose with blood concentration we can answer the original question of whether Agomelatine can feasibly block 5-HT2B at normal doses.

If anyone has taken a serotonin releaser with Agomelatine we'd like to hear from you!
 
It would be nice if this compound could be a sort of harm reduction or a good chem to have in the tool bag if your a frequent MDMA user or mephedrone ect
 
I just had the interesting idea after reading the thread about how novel RCs may develop (the future of research chemicals). What if someone were to make a prodrug of agomelatine and a drug which is an agonist for 5-ht2b? I am not such a big chemist so I wonder if this would be possible, but it would be interesting to see complimentary drugs combined as prodrugs with other drugs.
 
For some bizarre reason serotonin acting on 5-HT2B doesn't seem to cause any cardiac problems.
Click to expand...

I'm guessing that this has a lot to do with magnitude of binding affinity and synaptic concentration of ligand.

ebola
 
ebola? said:
I'm guessing that this has a lot to do with magnitude of binding affinity and synaptic concentration of ligand.

ebola
Click to expand...

Could be, 5-HT is quite potent though, and there's quite a bit around after chronic SSRI treatment. My unsubstantiated guess would be biased agonism.
 
there's quite a bit around after chronic SSRI treatment
Click to expand...

There's also marked downregulation of 5ht receptors (likely including the 2b isoform), perhaps attenuating the causal cascade underlying 5ht2b agonism's resulting cardiotoxicity in such cases. Then again, we might also expect such a mechanism to operate in the case of direct 5ht2b agonists too. . .

ebola
 
for the sake of the topic though, if a substance like agomelantine had a higher binding affinity than say mdma, and was taken and reached the receptors first, then the mdma was

ingested, and had less affinity, would this prevent the fibrosis/ hypertrophy of valves seen with 2b agonist? ( in theory)
 
You have to take into account relative concentrations too. Higher concentration of a lower affinity agonist can outcompete.

If you know the affinity for each at 5-HT2B, and the oral bioavailability of each, then you can figure out how much you would need to take for a particular dose of MDMA.

I guess you have to factor in the local 5-HT concentration as well, since that can drive the same sort of fibrosis apparently (thanks for that WSH).
 
T9358 said:
for the sake of the topic though, if a substance like agomelantine had a higher binding affinity than say mdma, and was taken and reached the receptors first, then the mdma was

ingested, and had less affinity, would this prevent the fibrosis/ hypertrophy of valves seen with 2b agonist? ( in theory)
Click to expand...

If you take a high enough dose of the 5-ht2b antagonist, then it would prevent both the cardiac and also the recreational effects of mdma, because both are mediated by 5-ht2b, so you would be better off just taking a placebo (it's cheaper ;)).
 
You must log in or register to reply here.
Top