Evaluation of in vivo binding properties of 3H-NMPB and 3H-QNB in mouse brain.
UNLABELLED: Apparent muscarinic acetylcholine (mAch) receptor occupancy in mouse cerebral cortex, hippocampus, and striatum by scopolamine, an antagonist, and biperiden, a relatively selective M1 antagonist, was estimated with competitive binding studies using two different radioligands: 3H-N-methyl piperidyl benzilate (3H-NMPB) and 3H-quinuclidinyl benzilate (3H-QNB). Both radioligands labeled mAch receptors in these brain regions, and the relative regional distributions of the specific binding of 3H-NMPB in vivo paralleled the distribution of mAch receptors. 3H-NMPB binding in vivo was much more sensitive to direct competitive inhibition by scopolamine than was 3H-QNB. A similar discrepancy in sensitivity to competitors between 3H-NMPB and 3H-QNB was also observed when biperiden was used as a competitor, indicating that binding to different subtypes of the mAch receptor could not account for the observed differences in sensitivity to competition. An in vivo saturation study suggested that the apparent association rate constant (k on) of 3H-QNB binding might be changed by ligand concentration. The heterogeneity of the free ligand concentration in intact brain was assessed in relation to the ligand concentration dependency of the apparent association rate constant (k on) of 3H-QNB binding. This finding, together with the more favorable accumulation of 3H-NMPB in cerebral cortex, hippocampus, and striatum, leads us to conclude that 3H-NMPB, or its positron emitting counterpart, should be the more favorable radiotracer for the estimation of mAch receptor occupancy by cholinergic drugs in the brain. KEYWORDS: mAch receptor, QNB, NMPB, in vivo, mouse.
T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T23 T24 T25 T26 T27 T28 T29 T2 T3 T4 T5 T6 T7 T8 T9
CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N GENE-Y GENE-N GENE-N GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
3H-NMPB acetylcholine 3H-quinuclidinyl benzilate 3H-QNB 3H-NMPB 3H-NMPB scopolamine 3H-QNB 3H-NMPB 3H-QNB 3H-QNB biperiden 3H-NMPB 3H-QNB mAch receptor mAch receptor M1 muscarinic acetylcholine (mAch) receptor mAch receptors mAch receptors mAch receptor scopolamine 3H-QNB 3H-NMPB 3H-NMPB biperiden QNB NMPB 3H-N-methyl piperidyl benzilate