In vitro and in vivo characteristics of [iodine-125] 3-(R)-quinuclidinyl (S)-4-iodobenzilate

J Nucl Med. 1989 Jun;30(6):1079-87.

Abstract

The radioiodinated muscarinic acetylcholine receptor antagonist, [125I] 3-quinuclidinyl 4-iodobenzilate, has two high affinity diastereomeric forms, the (R,R) and (R,S)-isomers. The (R,S)-diastereomer is only threefold lower in affinity than the (R,R)-isomer, but the kinetic properties are considerably different--the dissociation rate constant is 13-fold faster for the (R,S)-isomer and the association rate constant is two to threefold faster. The calculated affinity is therefore only fourfold lower. In vivo, the clearance of (R,S)-4IQNB from receptor-rich tissue is also more rapid than that of the (R,R)-isomer, that is a reflection of the more rapid in vitro kinetic properties since the physicochemical properties and the metabolic clearance of the diastereomers is the same.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism
  • Chemical Phenomena
  • Chemistry
  • Female
  • In Vitro Techniques
  • Iodine Radioisotopes*
  • Muscarinic Antagonists
  • Quinuclidines / pharmacokinetics*
  • Quinuclidinyl Benzilate* / analogs & derivatives*
  • Rats
  • Rats, Inbred Strains
  • Tissue Distribution

Substances

  • Iodine Radioisotopes
  • Muscarinic Antagonists
  • Quinuclidines
  • Quinuclidinyl Benzilate
  • 3-quinuclidinyl-4-iodobenzilate