RECEPTOR-BINDING CHARACTERISTICS OF [H-3]NAD-299, A NEW SELECTIVE 5-HT1A RECEPTOR ANTAGONIST

In vitro receptor binding properties of the novel tritiated 5-hydroxyt ryptamine(1A) (5-HT1A) receptor antagonist -[6-H-3]-3,4-dihydro-2H-1-b enzopyran-5-carboxamide ([H-3]NAD-299, generic name robalzotan) were e valuated and compared with those of the agonist 8-hydroxy-2-[2,3-H-3]d i-n-(propylamino)tetralin ([H-3]8-OH-DPAT). [H-3]NAD-299 binding displ ayed a K-d value of 0.17 nM and a B-max value of 26.7 pmol/g wet weigh t of rat hippocampus. Same binding affinity (K-d = 0.16 nM) was found to cloned human 5-HT1A receptors. Addition of the nonhydrolyzable GTP analog guanylylimidodiphosphate had no effect on the binding character istics of [H-3]NAD-299, while it significantly decreased both the affi nity and density of receptors labeled with [H-3]8-OH-DPAT. The rank or der of potency of various compounds to inhibit [H-3]NAD-299 binding is consistent with the labeling of 5-HT1A receptors. This newly develope d high-affinity and selective antagonist radioligand provides a valuab le tool for studies of 5-HT1A receptors both in vitro and in vivo. (C) 1998 Elsevier Science B.V. All rights reserved.