• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To register, simply click the Register button at the top right.

Serotonin 5HT-2C receptor antagonist Agomelatine


Senior Member
I was just researching the role of the 5HT-2C receptor in fatigue states and came across a drug, which is available in Europe and Australia, that might benefit those with sleep and neuroendocrine disturbances. The drug is called agomelatine. In addition to its activity at the 5HT-2C receptor, it is also a melatonin receptor agonist. Antagonism of the 5HT-2C receptor would have the effect of increasing dopamine and norepinephrine in the brain. There some evidence that the 5HT-2C receptor is UPregulated by cytokines, thereby reducing dopamine and norepinephrine and producing problems with mood, attention, alertness, etc.

Also, women receive two copies of the gene that codes for it while men receive only one.

Some more info here:




Senior Member
Do you mean that cytokines upregulate the receptor's expression? Peripherally or centrally? I have an interest in this area as well, but I worry about medications that have so many varied effects because if there is succes it is hard to attribute that success to one particular mechanism.

Licorice is an exampke of that - people claim it helps for all sorts of different reasons - adrenal support, salt loading of plasma, reduction in endothelial nitric oxide expression, central acetylcholine esterase activity? which one is it? LOL

I once met a guy who claimed that serotonin receptor agonists made his CFS much worse.

Lastly potent stimulation of some serotonin receptors by psychedelic medications such as DOM resulted in potent TNF alpha inhibition. Weird or what?