Posted by jrbecker on May 26, 2003, at 12:22:37
In reply to Re: You CANNOT lower CORTISOL directly » jrbecker, posted by CamW. on May 24, 2003, at 15:54:26
> Geez, I thought that Florian Holsboer had laid the CRF-antagonists research to rest. The only use they would be is in the initial treatment phase of depression, until standard therapies had a chance to kick in. Adjusting cortisol levels to relieve depressive symptoms just doesn't work.
>
> I also seem to remember that CRF-antagonists were tried (unsuccessfully) as anxiolytics.
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> Just thinking out loud. - CamHuh? It is my understanding that Holsboer is one of the biggest proponents of CRF1 antagonism R&D (please see below). I'd be very interested in hearing any news to the contrary. Thanks.
www.neurocrine.com/html/clin_anxietyDepression.html
Neurocrine Clinical Development Program Status
A first generation CRF1 non-peptide antagonist that was previously in development with Janssen Pharmaceutica (R121919) was studied in a Phase IIa clinical trial. This study, conducted by Dr. Florian Holsboer, Director of the Department of Psychiatry at the Max Planck Institute in Munich Germany, treated two groups of 20 patients suffering from major depression. Although the trial did not include a control placebo group and involved too few patients to draw definitive conclusions, a dose dependent improvement in measurements of both anxiety and depression were noted in 80% of patients providing the first indications of a CRF1 receptor antagonist effect using a novel mechanism for major depression. These results, "The First Human Experience with CRF Antagonists" were published in the Journal of Psychiatric Research and were presented at scientific meetings throughout 2000.
http://www.eneassoc.org/enea2002.htmProf. Florian Holsboer (Munich) demonstrated on the basis of CRH the way from basic research on depression to the development of novel therapeutical approaches in the treatment of this disease. Mice overexpressing CRH show signs and symptoms of affective disorders, whereas CRH receptor type-1 (CRHR1) knock-out mice show reduced anxiety-like behaviour. In vivo studies in innate high-anxiety rat strains with a novel CRHR1 antagonist (R121919) reduced anxiety-like behaviour. In patients with major depression R121919 was as effective as standard antidepressants. This indicates that CRHR1 antagonists represent powerful future tools for the individual pharmacological treatment of patients with affective disorders.
http://atlas.pharmalicensing.com/news/adisp/955314491_38f0f13bb4d9b
Florian Holsboer, M.D., Ph.D., and director at the Max Planck Institute fur Psychiatrie in Munich, Germany commented, "The results of an unrelated open label Phase IIa study conducted at the Max Planck Institute have provided encouraging results regarding the validity of the CRF mechanism as a potential therapeutic target for anxiety and depression.
http://www.cmeondemand.net/CNS/novelperspectives/CNS701_Holsboer.html
CRHR1 Antagonists as Novel Treatment Strategies
By Florian Holsboer, MD, PhD
Abstract
Research has provided considerable evidence for the hypothesis that corticotropin-releasing hormone (CRH), the key central coordinator of stress-hormone homeostasis, also plays a role in the development and course of depression and anxiety disorders. Studies using animal models of anxiety, as well as mouse mutants, in which the gene coding for the CRH type 1 receptor (CRHR1) was genetically deleted supported the notion that enhanced CRH/CRHR1 signaling underlies depression and anxiety disorders. Therefore, a number of small nonpeptide molecules that antagonize CRHR1 have been developed. In animal models, these molecules had anxiolytic and other stress-alleviating effects. An initial clinical study showed that CRHR1 antagonism has beneficial effects on depression and anxiety symptoms at doses unharmful to neuroendocrine stress responsivity.
poster:jrbecker
thread:228381
URL: http://www.dr-bob.org/babble/20030525/msgs/229225.html