Selective 5-HT2C agonists have shown antidepressant-like effects in several animal models of depression . Of the recently identified 5-HT2C agonists, Ro 60-0175, WAY-161503, and WAY-163909 have been the most extensively characterized in depression models. Results in chronic mild stress and olfactory bulbectomy models of depression suggest a more rapid onset of antidepressant action: typical antidepressants require 2-3 weeks of dosing to show effectiveness, while 5-HT2C agonists are active in less than one week in both models.
5-HT2C antagonists may also have a role in the treatment of depression. It has been shown that the 5-HT2C antagonists SB-242084 and RS 102221 potentiate the action of the SSRI citalopram on rat cortical and hippocampal 5-HT levels, although the 5-HT2C antagonists alone had no effect . It has also been claimed that the clinical antidepressant efficacy of agomelatine, a melatonin agonist, may be in part due to 5-HT2C antagonism .
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