robalzotan and 3-hydroxybenzylhydrazine

The receptor-mediated control of brain monoamine synthesis was used to examine the in vivo intrinsic efficacy of the 5-HT1A receptor antagonists NAD-299, S(-)-UH-301 and WAY-100,635. The rate of monoamine synthesis was estimated by measuring the accumulation of DOPA and 5-HTP in the ventral neostriatum and the ventral hippocampus in rats pretreated with an inhibitor of cerebral aromatic L-amino acid decarboxylase. S(-)-UH-301 (2.0-32.0 micromol kg(-1)), but not WAY-100,635 (0.08-1.2 micromol kg(-1)), produced a decreased 5-HTP accumulation in the neostriatum and in the hippocampus. The administration of NAD-299 (0.75-12.0 micromol kg(-1)) resulted in a slight increase in neostriatal, but not hippocampal, 5-HTP accumulation. Neostriatal DOPA accumulation was decreased by S(-)-UH-301, whereas treatment with WAY- 100,635 resulted in an increase. NAD-299 did not affect neostriatal DOPA levels. There were no effects by any of these agents on DOPA levels in the ventral hippocampus. It is concluded that S(-)-UH-301, but not WAY-100,635 or NAD-299, displays intrinsic efficacy at brain 5-HT1A and DA D2/3 receptors, whereas WAY-100,635 behaves as a DA D2/3 receptor antagonist. By this comparison, NAD-299 appears to be the most selective and specific 5-HT1A receptor antagonist.

Topics: 5-Hydroxytryptophan; 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Aromatic Amino Acid Decarboxylase Inhibitors; Benzopyrans; Brain Chemistry; Dihydroxyphenylalanine; Dose-Response Relationship, Drug; Enzyme Inhibitors; Hippocampus; Hydrazines; Male; Neostriatum; Piperazines; Pyridines; Rats; Rats, Sprague-Dawley; Receptors, Biogenic Amine; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Serotonin Antagonists