Having spent a few hours reviewing the Ki values for various drugs, as well as the claim that 5HT2c downregulation results in the disinhibition of NA and DA, the corresponding Ki value for agomelatine would suggest of course that, its not very strong at all.
Weaker than prozac...
And certainly in contrast to its affinity for melatonergic receptors, it could be said that NA implications are negligible.
Yet it's marketed as having a strong impact on NA....
But there was a poster that mentioned, in terms of the neurochemical implication, it can go beyond the Ki binding values - and they are not especially a definitive means to establish a drugs potency for implicating a specific neurochemical.
On that note - by example, having a look at Olanzapine - it has strong affinity for the alpha 2 adrenergic receptor, a blockade, which should theoretically positively effect NE levels.
As well as blockade at 2c serotonergic receptor subtype - again disinhibiting the release of NE.
Contrasting this to mirtazipine - exhibiting similar affinities for similar receptors - and claiming to be a, "NaSSA" - noradrenaline AD.
Also comparing the histamine blockade potency...
I mean, olanzapine is strong in that capacity, almost at a par with remeron.
So looking exclusively at their binding profiles, they should exhibit, in some manner, relatively similar modes of action.
But anecdotally, if you will, taking myself as an example, I showed - ZERO, response - of any kind, to olanzapine.
Did not assist with sleep - antihistamine action, did nothing.
Did not improve mood/energy - noradrenergic action.
Hell it even has a relative affinity for the M1 mACH receptor - and I didn't even get dry mouth, let alone orthostatic hypertension.
Mirtazipine - fantastic.
Great for sleep - antihistamine action.
Tremendous restoration of functionality - same mechanism of action on NE - alpha 2 blockade, 5ht2c blockade.
Forget serotonin - I don't respond to serotonergics.
So - this is a comparison made solely on the binding affinity Ki values.
Yet the contrast is obvious.
Very similar Ki values - very different results.
So what else exactly is there to take into consideration with these drugs, aside from their binding values, which impact the neurochemical balance - which is, from what I understand, their whole purpose and mode of action.
Please don't say, "they're just different...."
What is it about them that, despite similar values - yield very different results?
