Posted by pstrait on November 26, 2007, at 2:48:43
In reply to Re: New melatonergic antidepressant in USA trials, posted by mikez on November 21, 2007, at 14:54:46
RE: why is it a good idea to antagonize 5ht2c receptors
This abstract offers a theory of why 5ht2c antagonism is so important, including an explanation of why, under this theory, SSRIs work (and why they take weeks to work even though they are present in your brain more quickly and have non-AD effects more quickly).
I don't have immediate access to this journal but I am going to ILL it.
This may be promising for those who would benefit from Remeron/mirtazapine but can't deal with the weight gain etc. (unless of course those side effects are a direct consequence of 5ht2c antagonism -- but remeron also antagonizes 5ht2a, as well as alpha-2).
Also, if this does work well, it is pretty promising for some of the 5h52c inverse agonists in the works
Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies.
by
Millan MJ.
Institut de Recherches Servier,
Croissy-sur-Seine, France.
mark.millan@fr.netgrs.com
Therapie. 2005 Sep-Oct;60(5):441-60.ABSTRACT
Serotonin (5-HT)2C receptors play an important role in the modulation of monoaminergic transmission, mood, motor behaviour, appetite and endocrine secretion, and alterations in their functional status have been detected in anxiodepressive states. Further, 5-HT2C sites are involved in the actions of several classes of antidepressant. At the onset of treatment, indirect activation of 5-HT2C receptors participates in the anxiogenic effects of selective 5-HT reuptake inhibitors (SSRIs) as well as their inhibition of sleep, sexual behaviour and appetite. Conversely, progressive down-regulation of 5-HT2C receptors parallels the gradual onset of clinical efficacy of SSRIs. Other antidepressants, such as nefazodone or mirtazapine, act as direct antagonists of 5-HT2C receptors. These observations underpin interest in 5-HT2C receptor blockade as a strategy for treating depressive and anxious states. This notion is supported by findings that 5-HT2C receptor antagonists stimulate dopaminergic and adrenergic pathways, exert antidepressant and anxiolytic actions in behavioural paradigms, and favour sleep and sexual function. In addition to selective antagonists, novel strategies for exploitation of 5-HT2C receptors embrace inverse agonists, allosteric modulators, ligands of homo/heterodimers, modulators of interactions with 'postsynaptic proteins', dual melatonin agonists/5-HT2C receptor antagonists and mixed 5-HT2C/alpha2-adrenergic antagonists. Intriguingly, there is evidence that stimulation of regionally discrete populations of 5-HT2C receptors is effective in certain behavioural models of antidepressant activity, and promotes neurogenesis in the hippocampus. This article explains how these ostensibly paradoxical actions of 5-HT2C antagonists and agonists can be reconciled and discusses both established and innovative strategies for the exploitation of 5-HT2C receptors in the improved management of depressed and anxious states.
poster:pstrait
thread:795849
URL: http://www.dr-bob.org/babble/20071125/msgs/797096.html