Shinobu Akuzawa, Hiroyuki Ito and Tokio Yamaguchi
Neuroscience Research, Pharmacology Laboratories, Institute for Drug
Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 2I Miyukigaoka,
Tsukuba, Ibaraki 305-8585, Japan
Abstract: Characteristics of the binding of [3H]ramosetron
to cloned human 5-hydroxytryptamine3 (5-HT3) receptors
were investigated and directly compared to those of [3H]granisetron
binding. Saturation studies revealed that [3H]ramosetron labeled more sites
with high affinity (Kd=0.15+/-0.01 nM, Bmax=653+/-30
fmol/mg protein) than [3H]granisetron (Kd=1.17+/-0.25
nM, Bmax=427+/-43 fmol/mg protein). Kinetic studies revealed
that dissociation of [3H]ramosetron was slower than that of [3H]granisetron.
These results suggest that ramosetron is a highly potent 5-HT3-receptor
antagonist.
Keywords: Ramosetron, Granisetron, 5-HT3 receptor