A non peptidic corticotropin releasing factor receptor antagonist attenuates fever and exhibits anxiolytic-like activity
Autor: | Francois Jenck, Roya Teheranian, Zhen Chai, Homa Hasanvan, Johan Lundkvist, Ulrich Widmer, Tamas Bartfai, Jean-Luc Moreau |
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Rok vydání: | 1996 |
Předmět: |
Male
endocrine system medicine.medical_specialty Pituitary gland Fever medicine.drug_class Peptide hormone Biology Receptors Corticotropin-Releasing Hormone Rats Sprague-Dawley Mice Internal medicine Tumor Cells Cultured medicine Animals Pyrroles Receptor Pharmacology CP-154 526 Antagonist Biological activity Analgesics Non-Narcotic Receptor antagonist Recombinant Proteins Rats Pyrimidines Endocrinology medicine.anatomical_structure Anti-Anxiety Agents Cyclase activity Interleukin-1 medicine.drug |
Zdroj: | European Journal of Pharmacology. 309:195-200 |
ISSN: | 0014-2999 |
Popis: | The multiple actions of corticotropin-releasing factor (CRF) on neuroendocrine and behavioural functions can now be examined using new, high affinity, non peptidic antagonists which exhibit central activity upon systemic application. We have shown that compound CP 154,526 (butyl-ethyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo [2,3-d]pyrimidin-4-yl]amine) displaces [125I][Tyr0]CRF from rat hippocampal CRF receptors (IC50 = 0.5 nM) and from pituitary CRF receptors (IC50 = 0.04 nM). The same compound inhibits in a concentration-dependent manner the ovine CRF (0.1 microM)-stimulated adenylate cyclase activity in membranes of a mouse pituitary adenoma cell line, AtT20, with an IC50 value of 50 nM. Systemic application of the CRF receptor antagonist (0.16 mg/kg i.p.) blocked recombinant human interleukin-1 beta 5 micrograms/kg i.p.) induced fever in rats. The CRF receptor antagonist CP 154,526 (1 mg/kg i.p.) also exhibited signs of anxiolytic-like activity in the elevated plus-maze test in rats. |
Databáze: | OpenAIRE |
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