title: Autoradiographic localization and pharmacological characterization of [3H]tandospirone binding sites in the rat brain.
abstract: The regional distribution and pharmacological properties of [3H]tandospirone binding sites in the rat brain were investigated using quantitative autoradiography. [3H]Tandospirone binding was notably high in the dentate gyrus and CA1 area of the hippocampus, lateral septum, entorhinal cortex, interpeduncular nucleus and dorsal raphe nucleus. The distribution profiles of [3H]tandospirone binding sites significantly correlated with that of serotonin (5-HT)1A receptors identified using [3H]8-OH-DPAT. In competitive binding studies, [3H]tandospirone binding was inhibited by 5-HT, 8-OH-DPAT, pindolol, buspirone and N-(a,a,a-trifluoro-m-tolyl)-piperazine. The potencies of these ligands correlated with their affinities for 5-HT1A receptors. In addition, there was no significant difference in the dissociation constant of [3H]tandospirone binding between the dentate gyrus, CA1 area, dorsal raphe nucleus, lateral septum and entorhinal cortex (about 10 nM) suggesting that [3H]tandospirone binds to 5-HT1A receptors with same affinities in these brain structures. The distribution pattern of binding sites for [3H]tandospirone was also compared with that of benzodiazepine receptors identified using [3H]fludiazepam to find common effector sites for different types of anxiolytics. Some similarities were observed. It is evident in the hippocampal formation that an overlap of intense binding occurred. 5-HT1A receptors in the hippocampus may participate in the anxiolytic effects of tandospirone.
authors.affiliation: Research Laboratories, Sumitomo Pharmaceuticals Co., Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
authors.forename: Y
authors.initials: Y
authors.lastname: Kumasaka
authors.forename: A
authors.initials: A
authors.lastname: Hirose
authors.forename: T
authors.initials: T
authors.lastname: Tatsuno
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D014151:Anti-Anxiety Agents; D001345:Autoradiography; D001569:Benzodiazepines; D001665:Binding Sites; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D003975:Diazepam / Q000031:analogs & derivatives / Q000378:metabolism; D066298:In Vitro Techniques; D054833:Isoindoles; D008297:Male; D010879:Piperazines / Q000378:metabolism* / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D001569:Benzodiazepines; C055267:tandospirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C006107:fludiazepam; D003975:Diazepam