TRITIUM LABELLING OF DOPAMINE AGONIST: SCHIZOPHRENIA

点击翻译按钮获取中文摘要

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