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Antidepressant-like activity of corticotropin-releasing factor type-1 receptor antagonists in mice
- Source :
-
European Journal of Pharmacology . Sep2004, Vol. 499 Issue 1/2, p135-146. 12p. - Publication Year :
- 2004
-
Abstract
- The development of selective corticotropin-releasing factor type-1 (CRF1) receptor antagonists represents a potential novel treatment for depression. These studies evaluated CRF1 receptor antagonists for antidepressant-like activity in mice. Subchronic dosing of both R 121919 (3-[6-(dimethylamino)-4-methyl-pyrid-3-yl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidin-7-amine) and DMP 696 (4-(1,3-dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)-pyrazolo[1,5-a]-1,3,5-triazine) significantly decreased immobility time in the tail suspension test (at 30 and at 3 and 10 mg/kg, i.p., respectively). These antidepressant-like effects were observed at doses that did not impair general locomotor activity. Neither antalarmin (N-butyl-N-ethyl-[2,5,6-trimethyl-7-(2,4,6)trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine) nor DMP 904 (4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine) had an effect indicative of antidepressant-like activity. These results suggest that the tail suspension assay may have utility to identify CRF1 receptor antagonists with antidepressant-like activity. Moreover, the results lend support to the theory that some nonpeptidic CRF1 receptor antagonists may possess antidepressant-like activity and therefore represent a promising novel pharmacotherapeutic strategy in the treatment of depression. [Copyright &y& Elsevier]
- Subjects :
- *ADRENOCORTICOTROPIC hormone
*ANTIDEPRESSANTS
*DRUG therapy
*PEPTIDES
Subjects
Details
- Language :
- English
- ISSN :
- 00142999
- Volume :
- 499
- Issue :
- 1/2
- Database :
- Academic Search Index
- Journal :
- European Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 14376230
- Full Text :
- https://doi.org/10.1016/j.ejphar.2004.07.091