Pharmacological and Regional Characterization of [3H]LY278584 Binding Sites in Human Brain |
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| Authors: | Anissa Abi-Dargham Marc Laruelle David T Wong David W Robertson† Daniel R Weinberger Joel E Kleinman |
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| Institution: | Neuropathology Section, Clinical Brain Disorders Branch, IRP, NIMH Neuroscience Center at St. Elizabeths, Washington, D.C.;Lilly Research Laboratories, Eli Lilly and Company, California, U.S.A.;Lilly Corporate Center, Indianapolis, Indiana Ligand Pharmaceuticals, San Diego, California, U.S.A. |
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| Abstract: | Abstract: Binding of 3H]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 n M, 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 cortex. Specific binding was negligible in neocortical areas. Kinetic studies conducted in human hippocampus revealed a K on of 0.025 ± 0.009 n M −1 min−1 and a K off of 0.010 ± 0.002 min−1. The kinetics of 3H]LY278584 binding were similar in the caudate. Pharmacological characterization of 3H]LY278584 specific binding in caudate and amygdala indicated the compound was binding to 5-HT3 receptors. We conclude that 5-HT3 receptors labeled by 3H]LY278584 are present in both limbic and striatal areas in human brain, suggesting that 5-HT3 receptor antagonists may be able to influence the dopamine system in humans, similarly to their effects in rodent studies. |
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| Keywords: | 5-Hydroxytryptamine3 receptors [3H]LY278584 Limbic system Striatum |
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