Jpn. J. Pharmacol. 77 (1), 53-59 (1998)

Affinity of Mosapride Citrate, a New Gastroprokinetic Agent, for 5-HT4 Receptors in Guinea Pig Ileum

Takashi Yoshikawa, Naoyuki Yoshida, Yukiko Mine and Kanoo Hosoki

Discovery Research Laboratories I, Dainippon Pharmaceutical Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan

Abstract: We examined the binding affinity of mosapride citrate (mosapride) (4-amino-5-chloro-2-ethoxy-N-{[4-(4-fluorobenzyl)-2-morpholinyl]methyl}benzamide citrate), a novel gastroprokinetic agent, for the 5-hydroxytryptamine (5-HT) 4 receptors in guinea pig ileum using a selective 5-HT4-receptor radioligand, [3H]GR113808. In membrane preparations from longitudinal muscle with myenteric plexus in guinea pig ileum, specific [3H]GR113808 binding revealed a single saturable site of high affinity (Kd=0.28+/-0.02 nM, Bmax=45+/-3 fmol/mg protein). Mosapride and other 5-HT4-receptor agonists inhibited the specific binding of [3H]GR113808 in guinea pig ileum. The 5-HT4 agonists examined displayed the following inhibition potency order: BIMU-8 > cisapride > mosapride > renzapride > 5-HT > zacopride > metoclopramide. Mosapride exhibited monophasic inhibition of the specific [3H]GR113808 binding in the ileum (Ki value: 84.2 nM). The presence of mosapride (30 nM) significantly increased the Kd value to 0.44+/-0.05 nM in the Scatchard analysis of [3H]GR113808 binding. Bmax of [3H]GR113808, however, was not affected (48+/-4 fmol/mg protein) by mosapride. As for the affinity of mosapride, the addition of GppNHp (100 microM) slightly increased the Ki value to 104 nM. These results indicate that mosapride has an affinity for 5-HT4 receptors in guinea pig ileum in the radioligand binding study.

Keywords: Mosapride citrate, 5-Hydroxytryptamine (5-HT) 4 receptor, Gastrointestinal tract, Gastroprokinetic agent, Radioligand binding

Copyrightę The Japanese Pharmacological Society 1998

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