title: In vitro and in vivo characteristics of [iodine-125] 3-(R)-quinuclidinyl (S)-4-iodobenzilate.
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.
authors.affiliation: George Washington University Medical Center, Washington, DC.
authors.forename: R E
authors.initials: RE
authors.lastname: Gibson
authors.forename: T A
authors.initials: TA
authors.lastname: Schneidau
authors.forename: V I
authors.initials: VI
authors.lastname: Cohen
authors.forename: V
authors.initials: V
authors.lastname: Sood
authors.forename: J
authors.initials: J
authors.lastname: Ruch
authors.forename: J
authors.initials: J
authors.lastname: Melograna
authors.forename: W C
authors.initials: WC
authors.lastname: Eckelman
authors.forename: R C
authors.initials: RC
authors.lastname: Reba
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D018727:Muscarinic Antagonists; D011812:Quinuclidines / Q000493:pharmacokinetics*; D011813:Quinuclidinyl Benzilate / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
chemical_list: D007457:Iodine Radioisotopes; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D011813:Quinuclidinyl Benzilate; C040062:3-quinuclidinyl-4-iodobenzilate