[3H]linopirdine (DuP 996) labels a novel binding site in rat brain involved in the enhancement of stimulus-induced neurotransmitter release: autoradiographic localization studies.
A novel high-affinity binding site for linopirdine (DuP 996; 3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2-one), a cognitive enhancer which improves learning and memory in rodents and primates, has recently been identified in rat brain homogenates. [3H]Linopirdine binding sites were localized in rat brain using in vitro labeling, light microscopic autoradiography. Highest densities of binding sites were present in the hippocampus (CA1 to CA3 pyramidal cell layers and the granule cells of the dentate gyrus), the cerebral cortex (lamina IV), the dorsal raphe nucleus and the interpeduncular nucleus. Moderate densities were present in the olfactory bulb, olfactory tubercle, amygdala, subiculum and medial habenular nucleus. Lower levels of binding were present in the caudate/putamen, thalamus and hypothalamus. The localization of [3H]linopirdine binding sites in brain areas implicated in cognitive processes and affected in Alzheimer's disease suggest that ligands for this binding site may have therapeutic potential for the treatment of cognitive deficits seen in dementia.
Central Nervous System Diseases Research, Du Pont Merck Pharmaceutical Company, Wilmington, DE 19880.
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D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D007211:Indoles / Q000378:metabolism*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D007211:Indoles; D018377:Neurotransmitter Agents; D011725:Pyridines; D014316:Tritium; C061017:linopirdine