الفهرس يوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
Major depression is a type of depression characterized by persistent severe depressed mood for most of time for two-week period or more. Agomelatine, a novel antidepressant drug, is a melatonin analogue with a potent agonistic action on melatonin MT1 and MT2 receptors. It also has serotonin 5-HT2C receptor antagonistic activity. Although agomelatine is rapidly and well absorbed (> 75 %) after oral administration, it is subjected to an extensive first pass metabolism leading to a low absolute bioavailability (< 5%). The main objectives of the study are firstly to increase the absolute bioavailability of agomelatine and secondly to enhance its brain delivery. The nasal route was adopted to achieve these targets because the absorption from the nasal cavity is carried out into the systemic circulation avoiding the hepatic first pass metabolism which is expected to enhance absolute bioavailability of agomelatine. Also from the nasal cavity, agomelatine can be transported directly into the brain through the olfactory region of the nasal epithelium and the trigeminal neural region without having to cross the blood brain barrier (BBB). The direct nose to brain transport is expected to enhance its brain bioavailability and achieve brain targeting