Dopamine D-2 receptor imaging radiopharmaceuticals: synthesis, radiolabeling, and in vitro binding of (R)-(+)- and (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N- [(1-ethyl-2-pyrrolidinyl)methyl]benzamide

J Med Chem. 1988 May;31(5):1039-43. doi: 10.1021/jm00400a027.

Abstract

In developing central nervous system (CNS) dopamine D-2 receptor imaging agents, enantiomers, R-(+) and S-(-) isomers, of 3-[125I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2- pyrrolidinyl)methyl]benzamide, [125I]IBZM, were synthesized, and their in vitro binding characteristics were evaluated in rat striatum tissue preparation. The (S)-(-)-[125I]IBZM showed high specific dopamine D-2 receptor binding (Kd = 0.43 nM, Bmax = 0.48 pmol/mg of protein). Competition data of various ligands for IBZM binding displayed the following rank order of potency: spiperone greater than (S)-(-)-IBZM greater than (+)-butaclamol much greater than (R)-(+)-IBZM greater than (S)-(-)-BZM greater than dopamine greater than ketanserin greater than SCH23390 much greater than propanolol. The results indicate that [125I]IBZM binds specifically to the dopamine D-2-receptor with stereospecificity. The [123I]IBZM is potentially useful as an imaging agent for the investigation of dopamine D-2 receptors in humans.

Publication types

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

MeSH terms

  • Animals
  • Benzamides / chemical synthesis*
  • Benzamides / metabolism
  • Chemical Phenomena
  • Chemistry
  • Corpus Striatum / metabolism
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Male
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D2
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Benzamides
  • Iodine Radioisotopes
  • Pyrrolidines
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • 3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide