Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to evaluate the efficacy of agomelatine (S 20098) to accelerate reversal of the neuroendocrinological, behavioural and cyclical changes seen in a transgenic mouse model of the neuroendocrine characteristics of depression. The effects of agomelatine were assessed in transgenic mice with low glucocorticoid receptor (GR) function, after acute stress or induced phase shift, and compared to desipramine and melatonin. Mice were injected 2 h before the onset of the dark period with agomelatine (10 mg/kg, i.p.), desipramine (10 mg/kg, i.p.), melatonin (10 mg/kg, i.p.) or vehicle (hydroxy-ethyl-cellulose (HEC) 1%) each day for 21 to 42 days. Agomelatine was effective in reversing the transgenic mouse behavioural changes noted in the Porsolt forced swim test as well as in the elevated plus maze. Both the number of open arm entries and the total time spent in open arms of the elevated plus maze is greatly increased in transgenic mice. The mean time spent in open arms is exquisitely sensitive to reversal by agomelatine and desipramine. Agomelatine also markedly accelerated readjustment of circadian cycles of temperature and activity following an induced phase shift. This action of agomelatine was superior to that of melatonin while desipramine was without effect. The accelerating effect of agomelatine was particularly notable if treatment was started 3 weeks prior to the induced phase shift. Agomelatine treatment did not cause any major change in corticosterone or adrenocorticotropic hormone (ACTH) concentrations nor in vasopressin (AVP), corticotropin-releasing hormone (CRH), GR and mineralocorticoid receptor (MR) mRNAs levels, which make it unlikely that the mechanism of agomelatine action is related to hypothalamic-pituitary-adrenocortical (HPA) axis changes. The present study shows that agomelatine displays some characteristics of antidepressant drug action in the transgenic mouse model, effects that could be partially related to its chronobiotic properties.
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PMID:Antidepressant action of agomelatine (S 20098) in a transgenic mouse model. 1600 35

Antidepressant drugs were introduced into clinical practice in the mid-20th Century. While for the most part they have proven effective for the amelioration of depressive symptoms, they are associated with significant deficiencies. These well-recognized shortcomings have given impetus to the pursuit of new molecules that seek to improve on the efficacy, tolerability and safety of existing medications. The following article reviews several new compounds that may have antidepressant potential. Some are more advanced in development, having undergone clinical trials, whereas the clinical potential of others is yet to be explored. For this latter group of compounds, the antidepressant potential relies on their activity in validated animal models. Agomelatine and duloxetine are in the first category, having shown antidepressant efficacy in clinical trials. The blockade of cortisol secretion continues to be a focus of attention for the development of new antidepressants. Thus, synthesis inhibitors, nonpeptide antagonists of corticotropin-releasing factor and glucocorticoid receptor antagonists show some promise in clinical and preclinical tests. Antagonists of the neuropeptide substance P, vasopressin and neuropeptide Y represent a departure of approach from traditional monoamine receptor-based mechanisms. While the clinical results with one substance P antagonist have led to the cessation of further trials, other molecules are in development. Approaches to treatment based on glutamatergic transmission arose from observations in animal models. The clinical evaluation of such compounds awaits further development. The extent to which new agents can be judged to have met the goals of efficacy, tolerability and safety rely not only acute treatment trials but also on longer-term outcomes and postmarketing surveillance. Whether any of the new agents canvassed here prove to be significantly better than existing agents is clearly a judgement for the future.
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PMID:Emerging treatments for major depression. 1728 53