NEUROPHARMACOLOGY OF NEUROENDOCRINE AND NEUROTRANSMITTER REGULATORY MECHANISMS

神经内分泌和神经递质调节机制的神经药理学

• 批准号: 3781314
• 负责人: D L MURPHY
• 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/3781314
• 关键词: antidepressants; bulimia nervosa; buspirone; central neural pathway /tract; complementary DNA; hormone regulation /control mechanism; human genetic material tag; human subject; methylphenyltetrahydropyridine; migraine; neuroendocrine system; neuropharmacology; neurotoxins; neurotransmitter transport; neurotransmitters; norepinephrine; nucleic acid sequence; piperazines; prolactin; psychophysiology; serotonin; serotonin inhibitor; serotonin receptor; transport proteins

This project has continued to focus on investigations of the functional status of the serotonin (5-HT) neurotransmitter system in humans using 5_HT-selective agonists (e.g., m-chlorophenylpiperazine (m-CCP), buspirone) and antagonists (e.g., metergoline, ondansetron) as pharmacologic probes. In a collaborative study, a detailed analysis by Dr. T.D. Brewster of migraine-like late-onset headaches that occurred in a subject of younger females receiving m-CCP revealed: (1) headache responses were more frequent in patients with bulimia nervosa that controls; (2) severity of the headaches was related to higher plasma m- CCP plasma concentrations within these subjects; (3) however, as non- bulimic subjects populations had equally high plasma m_CCP concentrations, a state of post-synaptic 5-HT1C supersensitivity in cranial vasculations or other CNS structures may exist in a bulimic subgroup; and (4) a larger proportion of bulimic patients had blunted prolactin (but not cortisol) responses to m-CCP, suggesting a dissociation between the neuroendocrine and headache responses to m-CCP. In laboratory studies related to serotonin, a close structural analog of MPTP, (the dopamine neurotoxin which produces parkinsonism in several species), 2-NH-2-MPTP was found by Dr. Andrews to possess apparent serotonin and norepinephrine neurotoxicity and to lack effects on dopamine. Dr. K. Peter Lesch successfully isolated and sequenced a cDNA for the human 5-HT transport.

该项目继续专注于对功能的调查 使用人类中5-羟色胺（5-HT）神经递质系统的状态 5_ht选择性激动剂（例如，M-氯苯基哌嗪（M-CCP）， Buspirone）和拮抗剂（例如，纳斯特林（Metergoline），ondansetron） 药理学探针。 在一项协作研究中，由 发生在偏头痛的晚期头痛的T.D. Brewster博士发生 接受M-CCP的年轻女性的主题揭示了：（1）头痛 神经性贪食症患者的反应比 控件； （2）头痛的严重程度与较高的血浆M-有关 这些受试者中的CCP血浆浓度； （3）但是，非 - 大型受试者种群具有同样高的血浆M_CCP 浓度，突触后5-HT1C超敏的状态 颅骨血管或其他中枢神经系统结构可能存在 亚组； （4）较大比例的暴食患者钝了 催乳素（但不是皮质醇）对M-CCP的反应，这表明 神经内分泌和对M-CCP的头痛反应之间的解离。 在与5-羟色胺有关的实验室研究中，一个密切的结构类似物 MPTP（多巴胺神经毒素，在几种中产生帕金森氏症 物种），安德鲁斯博士发现2-NH-2-MPTP具有明显的 5-羟色胺和去甲肾上腺素神经毒性，缺乏对 多巴胺。 K. Peter Lesch博士成功地分离并测序了cDNA 对于人类的5-HT运输。