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RU-486 (mifepristone) -- Mechanism of Action » btnd

Posted by Shawn. T. on May 29, 2004, at 19:30:31

In reply to What is RU-486 ???, posted by btnd on May 29, 2004, at 18:28:07

Mifepristone (Corlux) is an antagonist at glucocorticoid type II receptors and progesterone receptors. Its mechanism of therapeutic action in psychotic depression involves glucocorticoid receptor antagonism. Cortisol, a key stress hormone, is an agonist at these receptors. I don't believe that a progesterone receptor antagonist would have beneficial effects in treating depression; perhaps a more selective glucocorticoid antagonist will eventually be made available.

Overactivity of the HPA axis has been reported in people with psychotic depression, but this fact alone does not help to explain the psychotic features of the disorder. One small study has suggested that the problem lies with an abnormal dopaminergic response to glucocorticoid receptor activation (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2798596), but this finding has not been replicated.
Compared to depression without psychotic features, psychotic depression has not been widely studied. Hopefully, the success of mifepristone in treating this disorder will convince researchers to investigate the possibility of a glucorticoid-dopamine connection and other potential abnormalities in glucocorticoid- related systems in psychotic depression in greater detail.

I'm not aware of any controlled clinical trials that have examined the usefulness of mifepristone for treating non-psychotic depression. Until these are available, I don't think that any conclusions about the use of the drug in this population should be jumped to.

Shawn


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poster:Shawn. T. thread:351716
URL: http://www.dr-bob.org/babble/20040527/msgs/351954.html