A Muscarinic Receptor Ligand: Review of the Chemistry and Applications
The radioiodinated analog of 3-quinuclidinyl benzilate (QNB) has been shown to bind to the mAChR by testing the saturability and the stereoselectivity in the corpus striatum, cerebellum, and the heart of rats. 3-Quinuclidinyl 4-iodobenzilate (4-IQNB) receptor binding can be inhibited by co-injection of small amounts of non-radioactive mAChR ligands as well as displaced by the same ligand after the 4-IQNB has bound to the receptor. Another important proof is obtained by using two stereomers of IQNB differing in the chirality at the quinuclidinyl carbon. The difference in distribution between the pharmacologically active form and the pharmacologically inactive form in those organs containing mAChR furnishes that proof. 4-IQNB was the first iodinated neuroreceptor-binding ligand to show high receptor to nonreceptor binding in man. More importantly, 4-QNB has been recently validated as a ligand showing a high correlation between the radioactivity in the target organ and the receptor concentration.