r-121919 has been researched along with Depressive-Disorder--Major* in 4 studies
2 review(s) available for r-121919 and Depressive-Disorder--Major
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Glucocorticoid receptor and treatment of psychotic major depression.
Topics: Animals; Brain; Dehydroepiandrosterone; Depressive Disorder, Major; Humans; Metyrapone; Mifepristone; Psychotic Disorders; Pyrimidines; Receptors, Corticotropin-Releasing Hormone; Receptors, Glucocorticoid | 2005 |
Recent advances in the neurobiology of depression.
Elucidation of the neurobiological basis of depression and other mood disorders is rapidly increasing. Considerable experimental and clinical evidence supports the fundamental roles of serotonin and norepinephrine, as well as the interactions between these systems in the etiology of depression. Substantial evidence has accrued, including changes in neurotransmitter and neurotransmitter metabolite concentrations, reuptake sites, and receptors, to support the hypothesis that alteration in neuronal serotonergic and noradrenergic function occurs in the central nervous system of patients with major depression. Serotonin and norepinephrine represent the major targets of current therapeutic interventions, which may induce longer-term adaptive changes via modulation of the activity of these neurotransmitters. In addition, two neuropeptide neurotransmitters--substance P and corticotropin-releasing factor--have been implicated in the pathophysiology of mood disorders. Preliminary studies have reported the clinical efficacy of a tachykinin NK1 receptor antagonist and a CRF1 receptor antagonist in depressive disorders. Further clarification of the precise neurobiological changes occurring in depression has implications for the use and development of novel effective treatments for this disorder. Topics: Antidepressive Agents; Depressive Disorder, Major; Humans; Norepinephrine; Pyrimidines; Receptors, Corticotropin-Releasing Hormone; Serotonin; Substance P | 2002 |
1 trial(s) available for r-121919 and Depressive-Disorder--Major
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Treatment with a CRH-1-receptor antagonist (R121919) does not affect weight or plasma leptin concentration in patients with major depression.
Weight gain during treatment with psychotropic drugs is frequently observed and is assumed to be responsible for non-compliance and for an elevated risk to develop a number of somatic co-morbidities including cardiovascular disorders and type 2 diabetes. Absence of weight inducing effects is therefore a major objective for the development of new compounds. Recently, R121919, the first corticotropin releasing hormone receptor 1 (CRH1R) antagonist, was tested in major depression. Clinical efficacy, safety, and tolerability of this compound could be demonstrated. Since CRH is discussed to be involved in the regulation of appetite and weight, directly and via interaction with leptin, CRH1R antagonists are suspected to influence body weight. Effects of 30 days of treatment with the CRH1R antagonist R121919 on weight and leptin levels in 20 patients suffering from major depression were investigated. No significant weight changes during treatment with R121919 were observed. Furthermore, noeffects on plasma leptin concentrations were found. We conclude that treatment with the CRH1R antagonist R121919 does not affect weight or plasma leptin concentrations in patients with major depression. Together with previous findings indicating safety, tolerability, and clinical efficacy CRH1R antagonists are highly promising as a new treatment option in depression. Topics: Adult; Depressive Disorder, Major; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Male; Middle Aged; Pyrimidines; Receptors, Corticotropin-Releasing Hormone; Receptors, Leptin; Risk Factors; Weight Gain | 2005 |
1 other study(ies) available for r-121919 and Depressive-Disorder--Major
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Selective corticotropin-releasing factor 1 receptor antagonist E2508 has potent antidepressant-like and anxiolytic-like properties in rodent models.
Corticotropin-releasing factor (CRF) is a hormone secreted by the hypothalamus in response to stress, and CRF antagonists may be effective for the treatment of stress-related disorders including major depressive and anxiety disorders. Here, we investigated the in vivo pharmacological profile of N-cyclopropylmethyl-7-(2,6-dimethoxy-4-methoxymethylphenyl)-2-ethyl-N-(tetrahydro-2H-pyran-4-ylmethyl)pyrazolo[1,5-a]pyridin-3-amine tosylate (E2508), a recently synthesized, orally active CRF1 receptor antagonist. Oral administration of a single dose of E2508 (3 or 10mg/kg), but not fluoxetine (30mg/kg), a selective serotonin reuptake inhibitor (SSRI), significantly shortened immobility time in rats in the forced swim test. E2508 (10, 30, or 100mg/kg) also showed an antidepressant-like effect in the forced swim test in mice, with no sedative or muscle relaxant effects for doses up to 100mg/kg. Moreover, E2508 (5 or 20mg/kg) significantly reduced anxiety-like behavior in the rat defensive burying test. Diazepam, a benzodiazepine anxiolytic agent, also showed an anxiolytic effect in the defensive burying test at the same dose that induced a muscle relaxant effect in mice. Administration of E2508 (30mg/kg) for 14 consecutive days did not affect sexual behavior. By contrast, fluoxetine (30mg/kg) administration for ≥7 consecutive days decreased sexual behavior. These results indicate that E2508 has both potent antidepressant-like and anxiolytic-like effects in rodent models, and is well tolerated compared with a commonly prescribed therapeutic SSRI or benzodiazepine. Topics: Acetylcholine; Administration, Oral; Animals; Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Cyclic AMP; Depressive Disorder, Major; Diazepam; Disease Models, Animal; Female; Fluoxetine; HEK293 Cells; Humans; Male; Mice; Mice, Inbred BALB C; Muscle Strength; Pyrazoles; Pyridines; Pyrimidines; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone; Selective Serotonin Reuptake Inhibitors; Sexual Behavior, Animal | 2016 |