Posted by Marty on December 21, 2008, at 1:15:03
In reply to Agomelatin: could 5HT(2c) action be bad for sleep?, posted by psychobot5000 on December 20, 2008, at 19:19:26
5-HT2c antagonism is activating, especially just before bed which is the case with Agomelatine. So activating as to become an obstacle to sleep.Ever read Prozac being the most activating of the SSRIs ? That's because it isn't an SSRI in the first place: Prozac main antidepressant mechanism of action is now recognized as being 5-HT2c antagonism. Prozac's SRI is only secondary and so today, because of it's rockstar status in the history of SSRI development, it's usually classified as an atypical SSRI.
Apart from Prozac and Agomelatine, most 5-HT2c antagonist usually benefit from some 5-HT2a antagonism which, contrary to 5-HT2c ANT, is very pro sleep.
It is my opinion that if someone on Agomelatine is sensitive to 5-HT2c antagonism to the point of rendering its MT1/MT2 agonistic action insufficient to sleep, adding an 5-HT2a antagonist could be a good move: it calms and improve sleep while being pro-DA in some regions of the brain where Agomelatine is also pro-DA. (A different kind of pro-DA that is. Not one that is even remotely as activating)
As I don't believe in DA antagonism in the treatment of depression, I'd go with low dose Trazodone (which is good regarding insomnia) instead of Seroquel or any other atypical neuroleptic. Trazodone metabolite m-CPP is reported to be an agonist of 5-HT2c and 5-ht2b, but is in fact a partial agonist weaker than serotonin at those receptors. m-CPP from 50 mg of metabolized Trazodone should be insignificant in the scheme of things.
Especially if you believe a 2003 study reporting Trazodone as having an 5-HT2c antagonistic profile equivalent to what's reported of Agomelatine.
(6.4 vs 6.2 pKi) ... But I, for one, call b*llsh*t on this one./\/\arty
poster:Marty
thread:869924
URL: http://www.dr-bob.org/babble/20081214/msgs/869976.html