In Vitro and In Vivo Characteristics of [Iodine-125] 3-(R)-Quinuclidinyl (S)-4-Iodobenzilate

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 considera...

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Published inThe Journal of nuclear medicine (1978) Vol. 30; no. 6; pp. 1079 - 1087
Main Authors Gibson, Raymond E, Schneidau, Timothy A, Cohen, Victor I, Sood, Virendar, Ruch, Jennifer, Melograna, John, Eckelman, William C, Reba, Richard C
Format Journal Article
LanguageEnglish
Published United States Soc Nuclear Med 01.06.1989
Subjects
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
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Summary: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.
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ISSN:0161-5505
1535-5667