Agomelatine interactions

[buildersoftime]

There doesn't seem to be much information about Agomelatine out there. As a fairly novel antidepressant, can anyone speculate on its potential interactions specifically with tryptamines, psychedelic phenethylamines and MDMA

 

[MagickalKat777]

Since it only seems to have affinity for melatonin receptors, I am curious about this as well.

 

[tyrael]

.... Agomelatine is a melatonergic agonist and a 5HT2c antagonist** (i.e., it has a unique mechanism of action). The melatonergic function appears to improve sleep patterns, whereas the serotonergic antagonism results in the release of norepinephrine and dopamine. Given the current information, the overall side-effect profile of agomelatine appears relatively mild.

....

Agomelatine has been empirically compared with a number of other antidepressants, including venlafaxine,14 paroxetine,16 and fluoxetine,18 with generally comparable clinical results. Additional studies19–21 attest to the general antidepressant efficacy of agomelatine, which has also been effective in the treatment of anxiety22,23 and seasonal affective disorder.24

Because of its effects on melatonin receptors, agomelatine purportedly improves overall sleep quality without daytime sedation.

....

Agomelatine appears to be well tolerated, have low rates of sexual dysfunction, exhibit no discontinuation syndrome, and be weight neutral. Agomelatine improves sleep and, at present, seems to be relatively safe in overdose. However, this antidepressant may cause elevations in hepatic enzymes—a finding that warrants further investigation.....

-- Agomelatine - A Novel Antidepressant

** Antagonism of the 5-HT2C receptor causes release of dopamine / norepinephrine.

....We investigated the effects of chronic treatment with agomelatine (an MT1/MT2 receptor agonist and 5-HT2C receptor antagonist) on the brain-derived neurotrophic factor (BDNF), fibroblast growth factor (FGF-2), and activity-regulated cytoskeleton-associated protein (Arc).....

BDNF and FGF-2 expression are both thought to be related to depressive states.

-- Modulation of neuroplastic molecules in selected brain regions after chronic administration of the novel antidepressant agomelatine

....Agomelatine is the first approved antidepressant that mediates its activity through the melatoninergic pathway rather than the monoaminergic system....

Efficacy of agomelatine in major depressive disorder: meta-analysis and appraisal



Just from a quick glance at the literature, it seems to be somewhat efficacious for mild depression. The real benefits however seem to really to be due to it's other properties (which the more common SSRIs/SNRIs/etc don't exhibit) which as assistance (opposed to the usual disturbance) with sleep patters, low rates of sexual dysfunction and (apparently none to very little) discontinuation syndrome effects.
It does look interesting possibly as a next gen AD.

With regard to Agomelatine and tryptamines/phenethylamines/MDMA; due to the effects on the melatonergic system - and the fact that melatonin has such a huge array of biological functions (including circadian rhythms [disorders] / learning and memory / mood [disorders] and obesity / metabolic systems ..... to name just a few) it wouldn't be surprising if there was some interaction there.



(if anyone wants the papers in full, let me know).

 

[endotropic]

In theory, a 5-HT2C antagonist would impair some aspects of the psychedelic experience, in theory.

 

[buildersoftime]

Would I be right to say that 5-HT2C antagonism could actually improve the psychedelic experience by reducing anxiety?

 

[dooble]

Some experiences with Agomelatine

Sorry to bring back up an old thread but I want to share my experiences with agomelatine.

What confuses me is, this should be a 'NDDI', but for example amitriptyline seems to have a much higher affinity for 5ht2c? I currently have tried 50mg to find out whether I can potentiate some other drugs. I do not plan to start taking this regularly, maybe in cycles. Will test liver values soon also.

First, on my last day of a two week 2mg clonazepam + 10mg chlordiazepoxide + 25mg amitriptyline + 3 beers a day cycle, I added 50mg agomelatine. I had acquired tolerance, did not feel the usual benzo high or amitriptyline's histamine knockout effect. Was yawning a bit though. I noticed potentiation of alcohol, tobacco and especially cannabis. Three beers got me way more drunk than previous nights. Then I smoked one cigarette (I am not a smoker) and the rush seemed more pronounced, really enjoyable.

But then, I smoked two bowls of cannabis mixed with tobacco and got pretty f'd up. I usually only smokes on weekends and am used to getting stoned, but this time I could not even walk straight. This is extremely unusual for me even with a lot of alcohol. Only pregabalin and alcohol puts me to this state.

Does dopamine play an important part in the function of benzos anyway?

Next day this experience was duplicated but I took 50mg DXM, and about 0,1mg bupe instead (plus three beers and 3 bowls of cannabis/tobacco). Again definite potentiation of alcohol and cannabis, but not sure about the bupe. I will try again without cannabis, then take a break and try later on with amphetamine.

Otherwise the only effect has been I wake up earlier feeling well rested, much unlike after amitriptyline's histamine nights.

Is the slight potentiation worth the money? Well, if future experiments prove this does indeed potentiate some drugs, why not keep it around. My doc won't even prescribe me moclobemide even though I show him studies which have safely combined high doses of amitriptyline and moclobemide.