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Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...

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Focused Ultrasound Induced Blood-Brain Barrier Opening for Targeting Brain Structures and Evaluating Chemogenetic Neuromodulation

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Progress in corticotropin-releasing factor-1 antagonist development.

Eric P Zorrilla¹, George F Koob

¹Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA. ezorrilla@scripps.edu

Drug Discovery Today

|March 9, 2010

Summary

Corticotropin releasing factor (CRF) receptor antagonists show promise for treating anxiety and addiction. Further research and clinical trials are ongoing to clarify their therapeutic potential for various conditions.

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Area of Science:

Neuroscience
Pharmacology
Endocrinology

Background:

Corticotropin-releasing factor (CRF) was isolated in 1981, leading to the pursuit of CRF receptor antagonists.
CRF(1) antagonists are being investigated for potential therapeutic applications beyond their mixed efficacy in treating depression.

Purpose of the Study:

To explore novel CRF(1) receptor antagonists based on an improved understanding of ligand-receptor interactions.
To identify chemically novel antagonists, including peptide-based, signal transduction-selective, and nonpeptide agents.

Main Methods:

Investigating the two-domain model of ligand-receptor interactions for CRF family receptors.
Identifying novel ligands with drug-like pharmacokinetic properties and adherence to the prevalent pharmacophore.
Monitoring clinical trials of small molecule CRF(1) antagonists.

Main Results:

Progress in understanding CRF receptor interactions may lead to chemically novel antagonists.
Novel ligands conforming to the pharmacophore and exhibiting favorable pharmacokinetics have been identified.
Several small molecule CRF(1) antagonists are in Phase II/III clinical trials.

Conclusions:

CRF(1) receptor antagonists represent a potential new class of pharmacotherapies, particularly for anxiety and addiction.
Further elucidation of ligand-receptor interactions could yield diverse CRF(1) antagonist structures.
The therapeutic utility of CRF(1) antagonists is expected to become clearer with ongoing clinical trials.