YM022, a highly potent and selective CCKBantagonist inhibiting gastric acid secretion in the rat, the cat and isolated rabbit glands

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Abstract
Summary—We investigated the effects of the novel CCKB/gastrin antagonist YM022 on gastric acid secretion in vivo and in vitro, compared to CI‐988 and L365.260 as reference antagonists. In the anaesthetized rat, pentagastrin‐induced stimulation of gastric acid secretion was dose‐dependently and up to 100% inhibited by iv administration of YM022 with an ID50of 0.009 ± 0.0006 μmol/kg h in comparison to 0.6 ± 0.03 and 3.40 ± 0.05 μmol/kg h for CI‐988 and L‐365,260, respectively. In the gastric fistula cat, iv administration of YM022 produced a similar inhibitory effect with an ID50of 0.02 μmol/kg in comparison to 1.6 and 2.5 μmol/kg for CI‐988 and L‐365,260, respectively. Furthermore, bolus injection of 0.6 μmol/kg YM022 produced 100% inhibition within 30 min and 85% inhibition was still observed after 3 h. In the isolated rabbit gastric glands, CCK8‐stimulated14C‐aminopyrine uptake was inhibited according to the following rank order of potency: YM022 (IC50= 0.0012 μM) ≫ CI‐988 (IC50= 0.2 μM) ≫ L365.260 (IC50= 2.8 μM). Unlike with L365.260, no influence of CI‐988 and YM022 on histamine‐stimulated acid output was shown in this study. Thus, YM022 is a highly potent and selective gastric CCK8/gastrin receptor antagonist and has a long‐lasting inhibitory effect on gastric acid secretion.

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