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 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.
Gibson
R E
RE
George Washington University Medical Center, Washington, DC.
Schneidau
T A
TA
Cohen
V I
VI
Sood
V
V
Ruch
J
J
Melograna
J
J
Eckelman
W C
WC
Reba
R C
RC
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
D007457:Iodine Radioisotopes; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D011813:Quinuclidinyl Benzilate; C040062:3-quinuclidinyl-4-iodobenzilate