67 The delay in antidepressant response makes it clear that the immediate effects of these drugs are not the main explanation of their antidepressant action, but gradual adaptive changes in neuronal responses might be ultimately responsible for the therapeutic benefits.68 Recent research with SSRIs and dual uptake inhibitors has shifted the research focus beyond the levels of receptors to those of protein kinase-mediated phosphorylation of transcription factors, which ultimately leads to changes in programs of gene expression.69 Considering the Inhibitors,research,lifescience,medical currently available drugs for antidepressant

treatment, there is now no doubt that the NE and 5-HT system are important in the pathophysiology and treatment of depression, as all the agents interact with one or both of these systems and the net effect is an increase in 5-HT neurotransmission.70 Future antidepressants will have to be developed Inhibitors,research,lifescience,medical with pharmacology directed at alternative neurotransmitters or neuromodulators, following novel mechanisms and hypotheses. For example, the involvement of γ-aminobutyric acid (GABA) in depression has long been suspected.71

Another example in the search for better treatment Inhibitors,research,lifescience,medical of depression has been the demonstration that a substance-P antagonist had an antidepressant activity equivalent to the SSRI paroxetine.72 Further targets for drugs include corticotropin-releasing factor (CRF; see the article by Holsboer Inhibitors,research,lifescience,medical in this issue73 ) or melatonin (see the article by Pevet in this issue74 ); these are currently under investigation and clinical results will be available in the near future. However, the “ideal” antidepressant {Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|Selleckchem Anti-infection Compound Library|Selleckchem Antiinfection Compound Library|Selleckchem Anti-infection Compound Library|Selleckchem Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|buy Anti-infection Compound Library|Anti-infection Compound Library ic50|Anti-infection Compound Library price|Anti-infection Compound Library cost|Anti-infection Compound Library solubility dmso|Anti-infection Compound Library purchase|Anti-infection Compound Library manufacturer|Anti-infection Compound Library research buy|Anti-infection Compound Library order|Anti-infection Compound Library mouse|Anti-infection Compound Library chemical structure|Anti-infection Compound Library mw|Anti-infection Compound Library molecular weight|Anti-infection Compound Library datasheet|Anti-infection Compound Library supplier|Anti-infection Compound Library in vitro|Anti-infection Compound Library cell line|Anti-infection Compound Library concentration|Anti-infection Compound Library nmr|Anti-infection Compound Library in vivo|Anti-infection Compound Library clinical trial|Anti-infection Compound Library cell assay|Anti-infection Compound Library screening|Anti-infection Compound Library high throughput|buy Antiinfection Compound Library|Antiinfection Compound Library ic50|Antiinfection Compound Library price|Antiinfection Compound Library cost|Antiinfection Compound Library solubility dmso|Antiinfection Compound Library purchase|Antiinfection Compound Library manufacturer|Antiinfection Compound Library research buy|Antiinfection Compound Library order|Antiinfection Compound Library chemical structure|Antiinfection Compound Library datasheet|Antiinfection Compound Library supplier|Antiinfection Compound Library in vitro|Antiinfection Compound Library cell line|Antiinfection Compound Library concentration|Antiinfection Compound Library clinical trial|Antiinfection Compound Library cell assay|Antiinfection Compound Library screening|Antiinfection Compound Library high throughput|Anti-infection Compound high throughput screening| remains to be discovered: it should

not only be effective and safe, but also be well tolerated and contribute to the overall well-being of the patient. Endocrine processes in depression A variety Inhibitors,research,lifescience,medical of hormonal abnormalities, such as altered levels of Cortisol, growth hormone (GH), or thyroid hormones, indicate the existence of endocrine disturbances, especially dysfunctions in the hypothalamuspituitary-adrenal (HPA) axis and/or the regulation of thyroid function. The consistent finding that a significant subpopulation Mephenoxalone of depressed patients hypersecrete Cortisol during the depressed state but not after recovery75 led to intensive investigation and analysis of the HPA system. The observations include hypersecretion of hypothalamic corticotropin-releasing hormone (CRH) and inadequate glucocorticoid feedback, increased Cortisol levels, and impaired suppression of the HPA axis in response to exogenous glucocorticoid administration.76-78 A more refined analysis recently led to formulation of the concept that impaired corticosteroid receptor signaling is a key mechanism in the pathogenesis of depression.79 Investigations of hormonal responses to noradrenergic stimulation provided useful information about the possible role of NE and pituitary and adrenal hormone secretion in depression.