In vitro and ex vivo evaluation of cyclic aminoalkyl benzilates as potential emission tomography ligands for the muscarinic receptor
| Autor: | S.E. Perry, Susan J. Fisher, Phillip S. Sherman, Charlotte A. Otto, R. Combs, G.K. Mulholland |
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| Rok vydání: | 1989 |
| Předmět: |
Brain Chemistry
Pathology medicine.medical_specialty Molecular Structure Chemistry Brain Mice Inbred Strains General Medicine Benzilates Receptors Muscarinic In vitro Quinuclidinyl Benzilate Kinetics Mice Pharmacokinetics Muscarinic acetylcholine receptor medicine Biophysics Animals Female Binding site Receptor IC50 Ex vivo Tomography Emission-Computed |
| Zdroj: | International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology. 16(1) |
| ISSN: | 0883-2897 |
| Popis: | A series of muscarinic antagonists were screened as potential receptor imaging agents. (+)2α-tropanyl benzilate (TRB), N-methyl-4-piperidyl benzilate (NMPB) and several analogs amenable to labeling with positron emitting isotopes were evaluated for muscarinic binding to mouse brain tissue in vitro and ex vivo using [3H]quinuclidinyl benzilate as the probe. The in vitro assay directly compared the innate binding affinities of the compounds. The rank order of binding (IC50) was TRB (0.7 nm), QNB (0.8 nm), scopolamine (1.3 nm) and NMPB (1.6 nm). The ex vivo assay was used to gain information regarding the pharmacokinetics and brain penetration of the compounds in live animals. Ex vivo results demonstrated that TRB was rapidly taken up into the brain and was equipotent with QNB in occupying muscarinic binding sites at early time points, but TRB binding decreased twice as fast over time as QNB binding. The results suggest TRB would be a good candidate for radiolabeling and further study. |
| Databáze: | OpenAIRE |
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