D1-receptor antagonists: comparison of [3H]SCH39166 to [3H]SCH23390.
A radiolabeled form of the benzonaphthazephine, SCH39166 was used to characterize the binding of this D1 antagonist in cortex, and an autoradiographic comparison of the localization of [3H]SCH39166 to [3H]SCH23390 (D1 antagonist and forerunner of SCH39166) binding was performed. The Kd for [3H]SCH39166, calculated from dissociation and association rate constants (1.09 nM), was comparable to the Kd value derived from Scatchard analyses of saturation data (1.74 nM). [3H]SCH39166 binds to brain tissue in a saturable manner with high affinity and low non-specific binding. Inhibition of [3H]SCH39166 binding by dopaminergic and serotonergic agents supports the hypothesis that this is indeed a D1-specific compound with little overlap onto serotonin (5-HT) receptors. The affinity of [3H]SCH39166 for 5-HT2 and 5-HT1c receptors is at least an order of magnitude lower than the affinity of [3H]SCH23390 for these same receptor sites. Quantitative autoradiographic analysis of [3H]SCH39166 and [3H]SCH23390 binding indicates high D1-receptor density in the caudate-putamen, nucleus accumbens, olfactory tubercle, substantia nigra and entopeduncular nucleus. Low levels of binding (not significantly above background) were detected with [3H]SCH39166 in lamina IV of the cortex and in choroid plexus; areas which had significant [3H]SCH23390 binding and are known to have a high density of 5-HT (5-HT2 and 5-HT1c respectively) receptors.
Alburges
M E
ME
Neuropsychiatric Research Institute, Fargo, ND.
Hunt
M E
ME
McQuade
R D
RD
Wamsley
J K
JK
D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000378:metabolism*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D007700:Kinetics; D008297:Male; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017366:Serotonin Receptor Agonists; C058081:ecopipam