(+/-)-7-chloro-8-hydroxy-1-(4'-[125I]iodophenyl)-3-methyl-2,3,4,5- tetrahydro-1H-3-benzazepine: a potential CNS D-1 dopamine receptor imaging agent

J Med Chem. 1989 Jul;32(7):1431-5. doi: 10.1021/jm00127a005.

Abstract

Synthesis, radiolabeling, and in vitro and in vivo properties of an iodinated benzazepine, (+/-)-7-chloro-8-hydroxy-1-(4'-[125I]iodophenyl)-3- methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, [125I]FISCH, as a potential imaging agent for evaluation of central nervous system (CNS) D-1 dopamine receptors in humans, were investigated. After an iv injection, this benzazepine derivative showed good brain uptake in rats (2.27, 1.40, 0.55% dose/whole brain at 2, 15, and 60 min, respectively). The striatum/cerebellum ratio was high (2.47 at 60 min after the injection). The binding affinity of this agent in rat striatum tissue preparation displayed a Kd of 1.43 +/- 0.15 nM. Competition data (in vitro) showed the following rank order of potency: SCH-23390 greater than (+/-)-FISCH greater than (+/-)-IBZP much greater than apomorphine greater than WB 4010 greater than ketanserin approximately spiperone. The preliminary data suggest that the agent is highly selective for the CNS D-1 receptor.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzazepines*
  • Brain / metabolism*
  • Chemical Phenomena
  • Chemistry
  • Humans
  • Iodobenzoates*
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine / metabolism
  • Receptors, Dopamine D1
  • Tissue Distribution

Substances

  • Benzazepines
  • Iodobenzoates
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • 7-chloro-8-hydroxy-1-(4'-iodophenyl)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine