In vivo competition studies with analogues of 3-quinuclidinyl benzilate.
Among ligands that bind to the alpha- and beta-adrenoceptors and to the muscarinic acetylcholine receptor (m-AChR), those that bind to the latter have the best properties for external detection of receptor sites by gamma-camera imaging. To develop the optimal radiotracer, nonradioactive analogues of 3-quinuclidinyl benzilate (I) were tested in in vivo displacement studies with (-)-[3H]I to determine their ability to compete with (-)-[3H]I for the muscarinic acetylcholine receptor. There is a linear correlation between the ability to compete with (-)-[3H]I for the m-AChR and the affinity constant of the analogue as determined by in vitro assay, suggesting that the test is a valid indicator of in vivo distribution. One radioiodinated analogue, 3-quinuclidinyl p- iodobenzilate , bound to m-AChR in the heart and brain of rats.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010276:Parasympatholytics / Q000378:metabolism; D011812:Quinuclidines / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000031:analogs & derivatives / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D010276:Parasympatholytics; D011812:Quinuclidines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011950:Receptors, Cholinergic; D017981:Receptors, Neurotransmitter; D011813:Quinuclidinyl Benzilate