Radiobrominated analog of SCH 23390, a selective dopamine D1 antagonist: Synthesis and biodistribution in mouse brain

SCH 23390 (R-(+)-8-chloro-2,3,4, 5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol) is a highly selective dopamine D1 antagonist. The authors have prepared an 8-bromo analog of SCH 23390 (BrSCH) labelled with Br-75 or Br-76 and have studied its distribution in mouse brain. Milligram quantities of BrSCH were synthesized by the reaction of its des-chloro analog with bromide in H/sub 2/O/sub 2/-glacial acetic acid. The product was purified by preparative HPLC and characterized by mass spectrometry, NMR, and a bioassay technique involving the inhibition of DA-induced vasodilation of dog renal artery. Comparison with an authentic sample confirmed that the product obtained was BrSCH. The time course of distribution of this drug in mouse brain was followed and the results showed high uptake in DA receptor-rich striatum. Striatum to cerebellum uptake ratios were observed to be as high as 25 two hours after injection. These results demonstrate that a positron-emitting radiobrominated analog of SCH 23390 would be useful in the imaging of cerebral dopamine D1 receptors