신경 스테로이드의 항우울 효과
Novel Antidepressants Targeting Neurosteroids
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Depressive disorders are prevalent worldwide. Despite the availability of various antidepressants, treatment responses remain suboptimal, with disappointing remission rates. Recent advancements in antidepressant development have shifted focus to mechanisms beyond traditional monoamine neurotransmitters, such as serotonin and norepinephrine. Allopregnanolone, a neurosteroid, acts as a positive allosteric modulator of GABAA receptors, playing a significant role in regulating mood and anxiety. Fluctuations in allopregnanolone levels during reproductive cycles contribute to mood disorders such as premenstrual dysphoric disorder, postpartum depression (PPD), and menopausal depression. Recently, the Food and Drug Administration approved two novel antidepressants, brexanolone (IV) and zuranolone (oral). These synthetic analogs of allopregnanolone offer fast-acting relief for PPD by enhancing GABAergic inhibition. Additionally, these neurosteroid-based therapies provide new hope for patients with depression beyond PPD, due to their rapid onset of action. However, concerns regarding long-term safety and the potential for misuse remain, necessitating further research. This review explores the relationship between neurosteroids and depression, with a focus on the mechanisms and clinical applications of brexanolone and zuranolone in treating mood disorders.
Abstract
Depressive disorders are prevalent worldwide. Despite the availability of various antidepressants, treatment responses remain suboptimal, with disappointing remission rates. Recent advancements in antidepressant development have shifted focus to mechanisms beyond traditional monoamine neurotransmitters, such as serotonin and norepinephrine. Allopregnanolone, a neurosteroid, acts as a positive allosteric modulator of GABAA receptors, playing a significant role in regulating mood and anxiety. Fluctuations in allopregnanolone levels during reproductive cycles contribute to mood disorders such as premenstrual dysphoric disorder, postpartum depression (PPD), and menopausal depression. Recently, the Food and Drug Administration approved two novel antidepressants, brexanolone (IV) and zuranolone (oral). These synthetic analogs of allopregnanolone offer fast-acting relief for PPD by enhancing GABAergic inhibition. Additionally, these neurosteroid-based therapies provide new hope for patients with depression beyond PPD, due to their rapid onset of action. However, concerns regarding long-term safety and the potential for misuse remain, necessitating further research. This review explores the relationship between neurosteroids and depression, with a focus on the mechanisms and clinical applications of brexanolone and zuranolone in treating mood disorders.
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