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Re: Fluoxetine = 5-HT2c Potent antagonist ? ..confused

Posted by JayBTV2 on August 6, 2008, at 10:20:57

In reply to Re: Fluoxetine = 5-HT2c Potent antagonist ? ..confused » rjlockhart '05, posted by Marty on August 6, 2008, at 9:29:58

I don't think 5-ht2c is the problem w/ SSRI sexual side-effects. Based on the fact that the new drug Agomelatine (Valdoxan) is supposed to a 5-ht2c antagonist and it _doesn't_ have the same sexual side-effect issues as most SSRIs.

See: http://www.ncbi.nlm.nih.gov/pubmed/18480691 :

A double-blind comparison of sexual functioning, antidepressant efficacy, and tolerability between agomelatine and venlafaxine XR.
Kennedy SH, Rizvi S, Fulton K, Rasmussen J.

Department of Psychiatry, University of Toronto, and University Health Network, 200 Elizabeth Street, Toronto, Ontario, Canada. sidney.kennedy@uhn.on.ca

Impaired sexual function is associated with major depressive disorder in the untreated state and is often more prevalent during antidepressant therapy, which frequently results in poor treatment compliance. In this double-blind, multicenter study, the effects of agomelatine (an MT1 and MT2 agonist and 5HT-2C antagonist) and venlafaxine XR on sexual function were compared using the Sex Effects Scale in depressed patients. A total of 276 male and female patients received either agomelatine (50 mg) or venlafaxine XR (titrated to a target dose of 150 mg/d) for 12 weeks. Those who were sexually active at baseline (n = 193) and those who, in addition, achieved remission (n = 111) were defined a priori for analyses of change in sexual function. Treatment-emergent sexual dysfunction was significantly less prevalent among patients who received agomelatine, and venlafaxine XR was associated with significantly greater deterioration on the Sex Effects Scale domains of desire and orgasm. Both treatments resulted in equivalently high rates of remission (agomelatine, 73%; venlafaxine XR, 66.9%), although fewer patients in the agomelatine group discontinued treatment because of adverse events (agomelatine, 2.2%, vs venlafaxine XR, 8.6%). Agomelatine seems to be an efficacious antidepressant with a superior sexual side effect profile compared with venlafaxine XR, although superiority to placebo was not evaluated in this trial.
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Agomelatine description from Wiki:


Agomelatine (Valdoxan, Melitor) is chemical compound that is structurally closely related to melatonin. Agomelatine is a potent agonist at melatonin receptors and an antagonist at serotonin-2C (5-HT2C) receptors, tested in an animal model of depression (forced swimming test in rodents). It is concluded that the antidepressant-like activity in this model most probably involves a combination of both its melatonin agonist and 5-HT(2C) receptor antagonist properties.


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