TRITIUM LABELLING OF DOPAMINE AGONIST: SCHIZOPHRENIA

这种化合物是由SRI为R. A博士合成的。 拉赫蒂，B 00。 马里兰州医学院精神病学教授 研究 多巴胺D4受体亚型是重要的，因为它们 可能与精神分裂症有关（我们报告了 精神分裂症大脑中的D4受体），注意力缺陷障碍， 和毒瘾 N-0437是唯一一种化学稳定， 多巴胺D2型激动剂 它以高亲和力结合到 多巴胺D2 D3和D4受体 配体如3 H阿扑吗啡 多巴胺也以这种方式结合，但非常不稳定， 在溶液中容易氧化，因此需要使用抗氧化剂 例如抗坏血酸，其可干扰结合。 3 H（-）NPA是 也可获得，但是是D4受体的部分激动剂。 （-） N-0347的对映异构体（W. Timmerman的博士论文）是一个高 多巴胺D2型受体的亲和部分激动剂。 在 造影剂（-）N-0437是完全的激动剂，其作用完全是高亲和力的 D2型受体。 我们开发了一个程序（Mol. 药学42：432-438 （1992））使用3 H激动剂和3 H拮抗剂来确定是否 药物是各种G的激动剂、部分激动剂或拮抗剂， 蛋白偶联受体 在这些研究中，我们使用[3 H]U-86170， 其从Upjohn公司获得。 不幸的是， [3 H]U-86170和[3 H] N-0437不再可用。 请求具有 已向NEN、阿默舍姆和托克里斯提供[3 H] N-0437，但他们 都没有成功 3 H（-）N-0437将是一种非常有用的放射性物质， 完全激动剂配体，并且是优选的配体，因为它与 对所有D2型受体都有很高的亲和力。 用户详细信息： 详细信息：用户编号：1711 Triotiation市，州：门洛帕克，加利福尼亚州 HPLC资金来源：NIH 3 N 01 MH 80015 NMR费用：$3539.46 2天 计划收入：$3539.46（预计）1复合

This chemical compound is being synthesized by SRI for Dr. R.A. Lahti, B00. of Psychiatry at Maryland School of Medicine. The study of dopamine D4 receptors subtypes is important because of their possible involvement in schizophrenia (we have reported increases in the D4 receptor in schizophrenic brains), attention deficit disorders, and drug addiction. N-0437 is the only chemically stable, full dopamine D2-type agonist available. It binds with high affinity to the dopamine D2, D3 and D4 receptors. Ligands such as 3H apomorphine and dopamine also bind in this manner but are highly unstable and readily oxidize in solution, thus requiring the use of antioxidants such as ascorbic acid which can interfere with binding. 3H(-)NPA is also available but is a partial agonist at the D4 receptor. The (-) enantiomer of N-0347 (Dr. W. Timmerman's PhD Thesis) is a high affinity partial agonist of the dopamine D2-type receptor. In contrast (-)N-0437 is a full agonist acting at high affinity at all D2-type receptors. We developed a procedure (Mol. Pharm. 42:432-438 (1992)) using a 3H agonist and a 3H antagonist to determine whether drugs are agonists, partial agonist, or antagonists at various G protein-coupled receptors. In those studies we used [3H]U-86170, which was obtained from the Upjohn Company. Unfortunately, both [3H]U-86170 and [3H] N-0437 are no longer available. Requests have been made to NEN, Amersham and Tocris to prepare [3H] N-0437, but they were unsuccessful. 3H(-) N-0437 will be a very useful radioactive full agonist ligand, and is the preferred ligand since it binds with high affinity to all the D2-type receptors. User Details: Experiment Details: User Number: 1711 Tritiation City, State: Menlo Park, CA HPLC Funding Source: NIH 3 N01 MH80015 NMR Charge: $3539.46 2 days Program Income: $3539.46 (projected) 1 compound