Posted by desolationrower on March 28, 2009, at 21:54:31
In reply to Re: Stopping w. AD or not? I am feeling better?, posted by bleauberry on March 27, 2009, at 14:36:10
i disagree with gilman about this. lack of SS doesn't mean a drug can't affect serotonin; mirtazapine is a strong 5ht2 antagonist, which is probably the most important set of receptors for SS. balance of 1a and 2 is one possible serotonin effect.
the study to look at would be this one,but i don't have a fulltext.
Mirtazapine (Mir) is a novel antidepressant, reported to raise extracellular noradrenaline (NA) through blockade of !2-autoreceptors and serotonin (5-HT) output via (1) indirect activation of facilitatory !1-adrenoceptors on the cell bodies of ascending 5-HT neurones and (2) blockade of presynaptic release-modulating !2-heteroreceptors on 5-HT terminals in the forebrain. To further assess the effect of Mir on NA/5-HT system interplay, including putative regional differences in the effects of the drug on 5-HT release in rat forebrain, we used in vivo microdialysis in anaesthetised rats. Probes were implanted in the dorsal hippocampus (DH) and frontal cortex (FCx), representing median and dorsal raphe 5-HT projection areas, respectively. In the DH, Mir (10 mg/kg s.c.) completely blocked the 5-HT release-suppressing action of the selective !2-adrenoceptor agonist clonidine (0.1 mg/kg s.c.), but had no effect per se on the 5-HT output. Neither drug significantly changed the 5-HT levels in the FCx. Mir perfused locally (10 µM via reverse-dialysis) also failed to significantly elevate 5-HT output, and did not affect the clonidine response in either brain area. Thus, the data confirm the basic !2-adrenoceptor-blocking properties of Mir, but are only partly concordant with previous studies reporting an increase of 5-HT output after Mir alone. Moreover, we find no elevation in 5-HT by the reference !2-adrenoceptor antagonist idazoxan (0.3-1.0 mg/kg s.c.). The discrepancies encountered, and the potential ability of !2-adrenoceptor antagonists in general to raise the output of 5-HT, are discussed with particular reference to methodological and other factors that may influence the experimental outcome (e.g., brain regional aspects, different !2-adrenoceptor subtypes, potential differences in adrenoceptor tone under varying experimental conditions).
-d/r
poster:desolationrower
thread:887227
URL: http://www.dr-bob.org/babble/20090322/msgs/887496.html