The binding of SCH 39166 and SCH 23390 to 5-HT1C receptors in porcine choroid plexus.
SCH 39166 is a novel benzonaphthazepine, which has been characterized as a potent and selective D1 antagonist. Recently, its D1 selective benzazepine predecessor, SCH 23390, has been shown to bind to 5-HT1C binding sites in the choroid plexus. Therefore, the present studies were undertaken to determine if SCH 39166 has any measurable affinity for 5-HT1C binding sites. Our results indicate that SCH 39166 exhibited poor affinity for the 5-HT1C receptor, with a Ki of 1327 nM. In contrast, SCH 23390 inhibited [3H]-mesulergine binding to 5-HT1C receptors with a Ki of 30 nM. The non-selective 5-HT antagonist, methysergide, inhibited binding with a Ki of 2.4 nM. Finally, studies with the stereoisomers of SCH 39166 and SCH 23390 demonstrated that stereoselectivity at the 5-HT1C site is significantly less than for the D1 site.
CV/CNS Pharmacology, Schering-Plough Research, Bloomfield NJ 07003.
L A
LA
Taylor
C E
CE
Tedford
R D
RD
McQuade
D000818:Animals; D000978:Antiparkinson Agents / Q000378:metabolism; D001552:Benzazepines / Q000378:metabolism*; D001667:Binding, Competitive; D002831:Choroid Plexus / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists; D004873:Ergolines / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism; D013552:Swine
D000978:Antiparkinson Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D004873:Ergolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C058081:ecopipam; C031649:mesulergine; D004298:Dopamine