Glucocorticoid receptors antidepressant mechanisms

Recent in vitro hybridization studies in the rat have demonstrated that t)rpical antidepressants increase the density of glucocorticoid receptors. Such an effect could increase the negative feedback mechanism and thereby reduce the s)mthesis and release of cortisol. In support of this hypothesis, there is preliminary clinical evidence that metyrapone (and the steroid s)mthesis inhibitor ketoconazole) may have antidepressant effects. Recently several lipophilic antagonists of corticotrophin releasing factor (CRT) type 1 receptor, which appears to be hyperactive in the brain of depressed patients, have been shown to be active in animal models of depression. Clearly this is a potentially important area for antidepressant development. 

Numerous other drugs have a myotoxic effect by various mechanisms, including antipsychotic and antidepressant drugs (e.g., olanzapine, clozapine) and drugs of abuse (e.g., cocaine, heroin, methamphetamine) that affect CNS and muscle dopamine and serotonin receptors fluoroquinolones glucocorticoids ... 

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