CLINICAL PHARMACOLOGY OF ANTIDEPRESSANTS

抗抑郁药的临床药理学

• 批准号: 3845208
• 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/3845208
• 关键词: ADP ribosylation; adult human (21+); alpha antiadrenergic agent; antidepressants; benzodiazepine receptor; bipolar depression; bipolar depression manic phase; blood chemistry; brain; cerebrospinal fluid; child (0-11); desipramine; dosage; drug metabolism; electroconvulsive therapy; endothelin; gas chromatography; hormone metabolism; human subject; human therapy evaluation; hydroxylation; leukocytes; lithium; lymphoblast; melatonin; mental disorder chemotherapy; neuroendocrine system; neuropeptide Y; neuropeptides; neurotransmitter metabolism; norepinephrine; pertussis toxin; platelets; psychopharmacology; somatostatin; somatotropin; tissue /cell culture

Highlights of clinical studies during the last year are: a) The first 20 subjects in the USA administered intravenous idazoxan, a selective alpha 2 antagonist, tolerated the drug well at doses producing selective and marked increases in the release of norepinephrine following an "orthostatic challenge." This provides a new tool for testing alpha 2 function. b) In severely depressed patients ECT selectively alters neuropeptide concentrations in cerebrospinal fluid such that endothelin, a probable modifier of signal transduction through several receptors, is markedly increased, neuropeptide Y is elevated and somatostatin is "normalized" while CRH and neurokinin A are unaffected. c) Platelets and leukocytes from lithium-treated manic-depressives show a significant reduction in the immunolabeling of G alpha q and an increase in pertussis toxin catalyzed [32P] ADP-ribosylation in cultured lymphoblasts from a separate group of bipolars. d) Despite the common classification as benzodiazepine agonists adinazolam and its n-desmethyl metabolite were found to have distinct pharmacodynamic spectrums of activity. Use of pharmacokinetic/pharmacodynamic modelling reveals wide differences in EC30 values for each of several effects - sedation ACTH/cortisol suppression, growth hormone release -suggesting that these are mediated by benzodiazepine receptor complexes with different properties.

去年临床研究的重点是： a) 美国的前 20 名受试者静脉注射了达唑克生，a 选择性α2拮抗剂，在产生剂量时对药物的耐受性良好 去甲肾上腺素释放选择性显着增加 “直立挑战”。 这为测试 alpha 2 提供了一个新工具 功能。 b) 在严重抑郁症患者中，ECT 选择性地改变神经肽 脑脊液中的浓度使得内皮素（可能是一种 通过几种受体的信号转导修饰剂，显着 增加，神经肽 Y 升高，生长抑素“正常化” 而 CRH 和神经激肽 A 不受影响。 c) 经锂治疗的躁狂抑郁症患者的血小板和白细胞显示 G alpha q 的免疫标记显着减少，并且增加 培养物中百日咳毒素催化的 [32P] ADP-核糖基化 来自另一组双相情感障碍的淋巴母细胞。 d) 尽管通常分类为苯二氮卓类激动剂 阿地唑仑及其 n-去甲基代谢物被发现具有独特的 药效学活性谱。使用 药代动力学/药效学模型揭示了 EC30 的巨大差异 几种效果中每种效果的值 - 镇静 ACTH/皮质醇抑制， 生长激素释放——表明这些是由 具有不同性质的苯二氮卓受体复合物。