T. Yoshikawa et al., AFFINITY OF MOSAPRIDE CITRATE, A NEW GASTROPROKINETIC AGENT, FOR 5-HT4 RECEPTORS IN GUINEA-PIG ILEUM, Japanese Journal of Pharmacology, 77(1), 1998, pp. 53-59
We examined the binding affinity of mosapride citrate (mosapride) [4-(
4-fluorobenzyl)-2-morpholinyl]methyl}benzamide citrate), a novel gastr
oprokinetic agent, for the 5-hydroxytryptamine (5-HT) 4 receptors in g
uinea pig ileum using a selective 5-HT4-receptor radioligand, [H-3]GR1
13808. In membrane preparations from longitudinal muscle with myenteri
c plexus in guinea pig ileum, specific [H-3]GR113808 binding revealed
a single saturable site of high affinity (K-d=0.28+/-0.02 nM, B-max=45
+/-3 fmol/mg protein). Mosapride and other 5-HT4-receptor agonists inh
ibited the specific binding of [H-3]GR113808 in guinea pig ileum. The
5-HT4 agonists examined displayed the following inhibition potency ord
er: BIMU-8 > cisapride > mosapride > renzapride > 5-HT > zacopride > m
etoclopramide. Mosapride exhibited monophasic inhibition of the specif
ic [H-3]GR113808 binding in the ileum (K-i value: 84.2 nM). The presen
ce of mosapride (30 nM) significantly increased the K-d value to 0.44/-0.05 nM in the Scatchard analysis of [H-3]GR113808 binding. B-max of
[H-3]GR113808, however, was not affected (48+/-4 fmol/mg protein) by
mosapride. As for the affinity of mosapride, the addition of GppNHp (1
00 mu M) slightly increased the K-i value to 104 nM. These results ind
icate that mosapride has an affinity for 5-HT4 receptors in guinea pig
ileum in the radioligand binding study.