MECHANISMS OF KINDLED SEIZURE SUPPRESSION BY CYSTEAMINE

半胱胺抑制癫痫发作的机制

• 批准号: 3922618
• 负责人: S NADI
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 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/3922618
• 关键词: aminoacid metabolism; brain metabolism; catecholamines; convulsions; cysteamine; dosage; drug administration routes; drug metabolism; glutamate receptor; laboratory rat; neurochemistry; neuromuscular disorder chemotherapy; neuropeptides; neuropharmacology; norepinephrine; receptor sensitivity; somatostatin

Cysteamine has been shown to suppress kindled seizures at doses from 90 mg/kg to 300 mg/kg when given to rats kindled to stage V. This project will involve the careful evaluation of the alterations in brain chemistry and the onset of the suppression of seizures in order to better understand the mechanism of action of cysteamine. The aims of he present project are to better understand the mechanisms by which cysteamine eliminates seizures. Rats which are kindled and sham operated will receive a single intraperitoneal injection of cysteamine (200 mg/kg). Following the administration of the drug, the animals will be observed for behavioral changes as well as seizure suppression. The rats will be killed at known time intervals following cysteamine administration, the brain removed, and the cortex, cerebellum, midbrain, pons-medulla, and hippocampus will be dissected. These tissues will be extracted and evaluated for peptide, amino acid, receptor, and catecholamine levels. The correlation of the chemical changes to the seizure suppression may allow the identification of one chemical alteration with a decrease in seizure activity. The next step in the study will be to determine if antagonists of the compound will also suppress seizures. Studies at present from our laboratory as well as others shown that both somatostatin and norepinephrine are decreased as a result of cysteamine administration. The results of the cysteamine experiments have shown that following administration of the drug, the suppression of seizures occurs not at the point where somatostatin is the lowest, but at a point where the levels of somatostatin are the closest to the control levels. These observations suggest that the suppression of the seizures following administration of the drug may be due to a receptor resensitization rather than the decrease of the somatostatin itself. Currently an investigation of the receptor activity and its interactions with other receptors is underway to better understand the mechanism of action of cysteamine.

半胱胺已被证明可以抑制一定剂量的癫痫发作 当给予第五阶段的大鼠时，剂量从 90 mg/kg 增加到 300 mg/kg。 该项目将涉及对变更的仔细评估 脑化学和癫痫发作抑制的发生 为了更好地了解半胱胺的作用机制。 当前项目的目的是更好地了解 半胱胺消除癫痫发作的机制。 老鼠是 点燃和假手术将接受一次腹膜内注射 注射半胱胺（200 mg/kg）。 继行政后 药物后，将观察动物的行为变化 以及抑制癫痫发作。 老鼠将在已知的时间被杀死 半胱胺给药后的时间间隔，大脑 去除了皮质、小脑、中脑、脑桥延髓和 海马体将被解剖。 这些组织将被提取并 评估肽、氨基酸、受体和儿茶酚胺 水平。 化学变化与癫痫发作的相关性 抑制可能允许识别一种化学变化 随着癫痫发作活动的减少。 研究的下一步 将确定该化合物的拮抗剂是否也会 抑制癫痫发作。 我们实验室目前也在研究 正如其他人所表明的，生长抑素和去甲肾上腺素都是 半胱胺给药后减少。 半胱胺实验结果表明： 给药后，不会抑制癫痫发作 在生长抑素最低的点，但在 生长抑素水平最接近对照水平。 这些观察结果表明，抑制癫痫发作 给药后可能是由于受体 重新敏化而不是生长抑素减少 本身。 目前正在研究受体活性和 它与其他受体的相互作用正在进行中，以更好地 了解半胱胺的作用机制。