ABSTRACT

Tandospirone (3aa, 4£, 7/J, 7aa-hexahydro-2-(4-(4-(2-pyrimidinyl> 1 -piperazinyl)-butyl-4, 7-methano-lH-iso-indole-l,3 (2H)-dione dihydrogen citrate) is a novel anxiolytic that has been marketed in Japan. Pharmacological profiles of tandospirone reveal that it exhibits few of the side effects, especially sedative effects on the central nervous system that are often seen by use of benzodiazepine derivatives (Shimizu et al, 1987). Previously, we reported that tandospirone induced flat-body posture in rat (Shimizu et al, 1992) and suppressed 5-HT metabolism (Tatsuno et al, 1989) in the rat brain. Furthermore, tandospirone displaced the specific binding of [3H]8-OH-DPAT to rat hippocampal membrane (Shimizu et al, 1988) and suppressed forskolin-stimulated cAMP in the rat hippocampus (Tanaka et al, 1995). These data strongly suggest that tandospirone is an agonist for rat 5-HT 1 A receptor. Although the intrinsic activity of tandospirone to rat 5-HTiA receptor is shown to be 0.86 by cAMP assay in the rat hippocampal membrane (Tanaka et al, 1995), it is well-known that several types of 5-HT receptor (5HTiA, 5HT4, 5HT7 etc.) are expressed in the hippocampus (Hoyer et al, 1994). In this context, it is important to elucidate the pure effects of tandospirone on the 5-HTiA receptor. Recently, several groups reported the sequence of 5-HT]

A receptor (Albeit et al, 1990; Fargin et al, 1988). In this study, we established a stable CHO cell line expressing human 5-HT!