CLINICAL PHARMACOLOGY OF ANTIDEPRESSANTS

抗抑郁药的临床药理学

• 批准号: 3859867
• 负责人: W Z POTTER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3859867
• 关键词: alpha antiadrenergic agent; alprazolam; antidepressants; benzodiazepines; bipolar depression; blood chemistry; blood proteins; clinical trials; desipramine; dioxins; drug administration rate /duration; drug metabolism; gas chromatography; human subject; human therapy evaluation; hydroxylation; intravenous administration; lithium; mass spectrometry; mental disorder chemotherapy; neuroendocrine system; norepinephrine; normetanephrine; psychopharmacology

Highlights of clinical studies during the last year are: 1. The alpha2 antagonist, idazoxan, has produced antidepressant effects only in bipolar and not in unipolar patients. Despite preclinical studies implicating a major role of brain alpha2 receptors in level of alertness relevant to sedation and learning, chronic idazoxan in healthy volunteers did not alter sedative and cognitive responses to alprazolam nor baseline indices of these parameters. An IND to administer intravenous idazoxan to patients and volunteers has been approved and a Phase I study of a more selective analogue, ethoxy-idazoxan is under way. 2. Biochemical studies on noradrenergic output measures in bipolar patients reveal a consistent relative elevation of the "extraneuronal" forms of norepinephrine and normetanephrine. Since we have shown that both lithium and alpha2-receptor blockade increase extraneuronal norepinephrine, a further link between the biochemistry of manic-depressive illness and drug action is suggested. 3. A completed study of intravenous adinazolam and its active metabolite, n-desmethyl adinazolam reveals differential effects of parent compound and metabolite on behavioral (sedation and cognitive impairment) and biochemical (ACTH and cortisol suppresion).

去年临床研究的重点是： 1. α2拮抗剂咪唑克生具有抗抑郁作用 仅适用于双相情感障碍患者，而不适用于单相情感障碍患者。 尽管进行了临床前研究 暗示大脑 α2 受体在警觉性水平中的主要作用 健康志愿者中与镇静和学习相关的慢性伊唑克生 不改变对阿普唑仑的镇静和认知反应，也不改变基线 这些参数的索引。 静脉注射咪唑克生的 IND 患者和志愿者已获得批准，并且一项更多的 I 期研究 选择性类似物乙氧基咪唑克生正在研发中。 2. 双相情感障碍去甲肾上腺素能输出测量的生化研究 患者表现出“神经元外”的一致相对升高 去甲肾上腺素和去甲变肾上腺素的形式。 既然我们已经证明了两者 锂和α2受体阻断会增加神经元外去甲肾上腺素， 躁狂抑郁症的生物化学与 建议采取药物治疗。 3. 静脉注射阿地唑仑及其活性代谢物的完整研究， n-去甲基阿地唑仑揭示了母体化合物和 行为代谢（镇静和认知障碍）和 生化（ACTH 和皮质醇抑制）。