PHARMACOLOGICAL AND REGIONAL CHARACTERIZATION OF [H-3] LY278584 BINDING-SITES IN HUMAN BRAIN

Binding of [H-3]LY278584, which has been previously shown to label 5-hydroxytryptamine3 (5-HT3) receptors in rat cortex, was studied in human brain. Saturation experiments revealed a homogeneous population of saturable binding sites in amygdala (K(D) = 3.08 +/- 0.67 nM, B(max) = 11.86 +/- 1.87 fmol/mg of protein) as well as in hippocampus, caudate, and putamen. Specific binding was also high in nucleus accumbens and entorhinal conex. Specific binding was negligible in neocortical areas. Kinetic studies conducted in human hippocampus revealed a K(on) of 0.025 +/- 0.009 nM-1 min-1 and a K(off) of 0.010 +/- 0.002 min-1. The kinetics of [H-3]LY278584 binding were similar in the caudate. Pharmacological characterization of [H-3]LY278584 specific binding in caudate and amygdala indicated the compound was binding to 5-HT, receptors. We conclude that 5-HT3 receptors labeled by [H-3]LY278584 are present in both limbic and striatal areas in human brain, suggesting that 5-HT, receptor antagonists may be able to influence the dopamine system in humans, similarly to their effects in rodent studies.