CLINICAL PHARMACOLOGY OF ANTIDEPRESSANTS

抗抑郁药的临床药理学

• 批准号: 3781361
• 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/3781361
• 关键词: adolescence (12-20); adrenergic receptor; adult human (21+); alpha antiadrenergic agent; antidepressants; benzodiazepines; blood chemistry; brain; catecholamine inhibitor; child (0-11); clinical depression; clinical trials; cyclic AMP; desipramine; drug interactions; drug metabolism; drug receptors; epinephrine; forskolin; gas chromatography; human subject; human therapy evaluation; hydroxylation; melatonin; mental disorder chemotherapy; neuroendocrine system; neuropharmacology; norepinephrine; pediatric pharmacology; pharmacokinetics; platelets; psychopharmacology; sedative /hypnotic

Studies during the last year were focussed in these area: a) Plasma catecholamine responses in humans following intravenous administration of an alpha2 antagonist, idazoxan, have been characterized and shown to be highly correlated, not with the density of platelet alpha2 receptors but the shape of the epinephrine mediated inhibition of forskolin stimulated cyclic-AMP. This provides the first evidence in humans that an integrated physiologic response which as norepinephrine release to an alpha2 antagonist may be predicted on the basis of the functional state of alpha2 receptors on platelets. Application to populations with affective illness in which alpha2 function may be abnormal is underway. b) Since idazoxan binds to non-alpha2 so-called imidazoline sites, there is a possibility that some of its effects do not reflect antagonism of alpha2 receptors. Under our direction a Phase I study of a truly selective analogue that does not bind to other sites, ethoxy idazoxan, has been successfully completed in the United Kingdom. Based on this data, we are in the process of obtaining an IND to administer to humans in this country. c)We obtained and administered U-78875, a compound with mixed benzodiazepine agonist/antagonist activity to 10 healthy volunteers in an attempt to separate sedative from neuroendocrine effects and model pharmacodynamic response vs drug concentration. Data analyses are still underway.

去年的研究集中在以下领域： a) 静脉注射后人体血浆儿茶酚胺反应 α2拮抗剂咪唑克生的给药已得到表征 并显示与血小板密度高度相关 α2 受体，但肾上腺素介导的抑制的形状 毛喉素刺激环磷酸腺苷。 这提供了第一个证据 人类认为一种综合的生理反应，如去甲肾上腺素 α2拮抗剂的释放可以根据 血小板上α2受体的功能状态。 申请到 患有情感疾病的人群，其中 alpha2 功能可能受到影响 异常正在进行中。 b) 由于咪唑克生与非 alpha2 所谓的咪唑啉位点结合，因此 其某些效应有可能并不反映拮抗作用 α2受体。 在我们的指导下，一项真正的第一阶段研究 不与其他位点结合的选择性类似物，乙氧基咪唑克生， 已在英国顺利完成。 基于此 数据，我们正在获得用于人类的 IND 在这个国家。 c)我们获得并施用了U-78875，一种混合​​了 对 10 名健康志愿者进行苯二氮卓类激动剂/拮抗剂活性 尝试将镇静剂与神经内分泌作用和模型分开 药效反应与药物浓度。 数据分析仍在 进行。