MECHANISMS OF KINDLED SEIZURE SUPPRESSION BY CYSTEAMINE

半胱胺已被证明在剂量上能抑制点燃的癫痫 从90 mg/kg到300 mg/kg，用于点燃到V期的大鼠。 这个项目将涉及对改造的仔细评估。 脑化学与癫痫发作抑制的开始 以便更好地了解半胱胺的作用机制。 这个项目的目的是为了更好地了解 半胱胺消除癫痫发作的机制。老鼠是 点燃和假手术将收到单一的腹膜内注射 注射半胱胺(200 mg/kg)。追随政府 在药物的作用下，将观察动物的行为变化 以及抑制癫痫发作。这些老鼠将在已知时间被杀死 半胱胺给药后的时间间隔，大脑 切除大脑皮质、小脑、中脑、脑桥-髓质和 海马体将被解剖。这些组织将被提取出来并 多肽、氨基酸、受体和儿茶酚胺的评估 级别。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 将确定化合物的拮抗剂是否也会 抑制癫痫发作。目前我们实验室的研究也是如此 另一些研究表明，生长抑素和去甲肾上腺素都是 由于服用半胱胺而减少。 半胱胺实验的结果表明： 给药后，对癫痫发作的抑制作用不会发生 在生长抑素水平最低的时候，但在 生长抑素水平最接近对照水平。 这些观察表明，对癫痫发作的抑制 用药后可能与受体有关 生长抑素的再增敏而不是减少 它本身。目前对受体活性和受体活性的研究 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。

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.