CRH-sub-1 receptor antagonists for the treatment of depression and anxiety

Experimental and Clinical Psychopharmacology
Marcus Ising, Florian Holsboer

Abstract

From basic and clinical studies, ample evidence has emerged that abnormalities of stress hormone regulation observed in depression and anxiety are caused by elevated secretion of hypothalamic corticotropin-releasing hormone (CRH). This neuropeptide acts through CRH1 receptors to produce a number of anxiety- and depression-like symptoms, which has resulted in extensive validation of CRH1 receptors as a potential drug target. A number of orally available nonpeptidergic small molecules that are able to pass the blood-brain barrier have been discovered. Some of these compounds have entered clinical development. The authors summarize results from clinical studies of 2 CRH1 antagonists. One study designed as a safety and tolerability study also monitored amelioration of depression under 2 dose-escalation regimens. The compound studied, NBI-30775/R121919, was found to have a clinical profile comparable to that of paroxetine. In a second study the effect of another CRH1 antagonist, NBI-34041, on stress hormone secretion in response to a psychosocial stressor was investigated. Administration of this compound to healthy controls was found to reduce the stress-elicited secretion of stress hormones. However, neither compound impaired the C...Continue Reading

Citations

Jul 21, 2009·Current Gastroenterology Reports·Yvette TachéAndreas Stengel
Oct 27, 2010·International Journal of Pediatric Endocrinology·Stephanie A StoutDavid E Sandberg
Jul 16, 2010·International Journal of Endocrinology·Marcella BalboEve Van Cauter
Oct 1, 2010·Experimental Biology and Medicine·Andreas Stengel, Yvette Taché
Jul 13, 2011·Journal of Pharmacological and Toxicological Methods·S D KatugampolaC Da Costa Mathews
Jul 1, 2009·Pharmacology & Therapeutics·Sonja Horstmann, Elisabeth B Binder
Sep 9, 2008·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·P HeiserH Vedder
Aug 5, 2008·Trends in Neurosciences·Carmine M Pariante, Stafford L Lightman
Jul 10, 2008·International Journal of Geriatric Psychiatry·Eric J Lenze, Julie Loebach Wetherell
Mar 10, 2009·Brain, Behavior, and Immunity·Leonardo H TonelliTeodor T Postolache
May 21, 2013·Psychoneuroendocrinology·Fabrice DuvalMarc-Antoine Crocq
Mar 23, 2010·International Clinical Psychopharmacology·Giorgio Racagni, Maurizio Popoli
Nov 14, 2008·Stress : the International Journal on the Biology of Stress·Karen L SmithDavid P Finn
Jul 21, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Ryan BogdanAhmad R Hariri
Jan 1, 2011·Personalized Medicine·Torsten Klengel, Elisabeth B Binder
Aug 8, 2009·Trauma, Violence & Abuse·Gretchen N NeighCharles B Nemeroff
Jul 20, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·Qingzhong Wang, Yogesh Dwivedi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Related Papers

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Florian Holsboer
Annals of the New York Academy of Sciences
E ZoumakisG P Chrousos
Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Stephen C HeinrichsD E Grigoriadis
© 2021 Meta ULC. All rights reserved