Preparation and biodistribution of 1-[2-(3-[125I]iodo-4-aminophenyl)ethyl]-4-[3-(trifluoromethyl) phenyl]piperazine and 1-[2-(3-[125I]iodo-4-azidophenyl)ethyl]-4-[3-(trifluoromethyl)phenyl] piperazine

J Med Chem. 1989 Mar;32(3):543-7. doi: 10.1021/jm00123a006.

Abstract

The iodinated analogue of 1-[2-(4-aminophenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]piperazine (PAPP), IPAPP (4), and the corresponding azido compound azido-IPAPP (5) were synthesized. The corresponding no-carrier-added 125I (T1/2 = 60 days, 35-60 keV) labeled compounds were also prepared. High specific binding was observed from in vitro binding studies using rat brain tissue preparation; Ki = 20 and 17.5 nM against [3H]-5-HT. In vivo biodistribution studies in rats showed that azido-[125I]IPAPP passed through intact blood-brain barrier and localized in the brain. Ex vivo autoradiography of rat brain sections exhibited a diffuse uptake pattern, which may be due to specific and nonspecific binding. The results indicate that IPAPP and azido-IPAPP may not be suitable to image the serotonin receptor in the brain.

MeSH terms

  • Animals
  • Autoradiography
  • Azides / chemical synthesis*
  • Azides / pharmacokinetics
  • Binding, Competitive
  • Brain / metabolism
  • Cattle
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Isotope Labeling
  • Male
  • Piperazines / chemical synthesis*
  • Piperazines / pharmacokinetics
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / metabolism
  • Tissue Distribution

Substances

  • Azides
  • Iodine Radioisotopes
  • Piperazines
  • Receptors, Serotonin
  • 1-(2-(3-iodo-4-aminophenyl)ethyl)-4-(3-(trifluoromethyl)phenyl)piperazine
  • 1-(2-(3-iodo-4-azidophenyl)ethyl)-4-(3-(trifluoromethyl)phenyl)piperazine