title: Receptor binding characteristics of [3H]NAD-299, a new selective 5-HT1A receptor antagonist.
abstract: In vitro receptor binding properties of the novel tritiated 5-hydroxytryptamine1A (5-HT1A) receptor antagonist (R)-3-N,N-dicyclobutylamino-8-fluoro-[6-3H]-3,4-dihydro-2H-1-benzo pyran-5-carboxamide ([3H]NAD-299, generic name robalzotan) were evaluated and compared with those of the agonist 8-hydroxy-2-[2,3-3H]di-n-(propylamino)tetralin ([3H]8-OH-DPAT). [3H]NAD-299 binding displayed a Kd value of 0.17 nM and a Bmax value of 26.7 pmol/g wet weight of rat hippocampus. Same binding affinity (Kd = 0.16 nM) was found to cloned human 5-HT1A receptors. Addition of the nonhydrolyzable GTP analog guanylylimidodiphosphate had no effect on the binding characteristics of [3H]NAD-299, while it significantly decreased both the affinity and density of receptors labeled with [3H]8-OH-DPAT. The rank order of potency of various compounds to inhibit [3H]NAD-299 binding is consistent with the labeling of 5-HT1A receptors. This newly developed high-affinity and selective antagonist radioligand provides a valuable tool for studies of 5-HT1A receptors both in vitro and in vivo.
authors.affiliation: Department of Lead Generation, Preclinical R & D, Astra Arcus, Södertälje, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Jerning
authors.forename: G T
authors.initials: GT
authors.lastname: Svantesson
authors.forename: N
authors.initials: N
authors.lastname: Mohell
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D006150:Guanine Nucleotides / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007477:Ions; D007700:Kinetics; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000378:metabolism* / Q000494:pharmacology; D014162:Transfection; D014316:Tritium
chemical_list: D001578:Benzopyrans; D006150:Guanine Nucleotides; D007477:Ions; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D014316:Tritium; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C108607:robalzotan