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Corticotropin-releasing hormone modulators and depression
1Max Planck Institute of Psychiatry, Kraepelinstrasse 10, 80804 Munich, Germany. holsboer@mpipsykl.mpg.de
Current Opinion in Investigational Drugs (London, England : 2000)
|March 11, 2003
Summary
Overactive central corticotropin-releasing hormone (CRH) circuits are linked to depression. CRH-type 1 receptor antagonists show promise for treating depression by reducing CRH signaling.
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatry
Background:
- Central corticotropin-releasing hormone (CRH) circuits are overactive in depression.
- This hyperactivity is associated with elevated peripheral cortisol and corticotropin levels.
- CRH overexpression contributes to depression's characteristic signs and symptoms.
Purpose of the Study:
- To investigate the role of CRH-type 1 receptors (CRHR1) in mediating depression-related symptoms.
- To evaluate the efficacy of CRHR1 antagonists as a potential antidepressant treatment.
Main Methods:
- Development of small molecule CRHR1 antagonists designed to cross the blood-brain barrier.
- Testing these compounds in animal models of depression and in clinical trials with human patients.
- Assessment of depressive symptomatology and adverse effects.
Main Results:
- CRHR1 antagonists selectively bind to CRHR1 with high affinity, reducing CRH signaling.
- One compound, R-121919, effectively ameliorated depressive symptoms in clinical studies.
- R-121919 demonstrated no significant endocrine or other adverse effects.
Conclusions:
- CRHR1 antagonists represent a promising therapeutic strategy for major depression.
- While R-121919 trials were discontinued, ongoing development of other CRHR1 antagonists may offer novel antidepressant alternatives.