TY - JOUR
T1 - YM022, a highly potent and selective CCK(B) antagonist inhibiting gastric acid secretion in the rat, the cat and isolated rabbit glands
AU - Attoub, S.
AU - Moizo, L.
AU - Laigneau, J. P.
AU - Alchepo, B.
AU - Lewin, M. J.M.
AU - Bado, A.
PY - 1998
Y1 - 1998
N2 - We investigated the effects of the novel CCK(B)/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 ID50 of 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 ID50 of 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-stimulated 14C- 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 CCK(B)/gastrin receptor antagonist and has a long-lasting inhibitory effect on gastric acid secretion.
AB - We investigated the effects of the novel CCK(B)/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 ID50 of 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 ID50 of 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-stimulated 14C- 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 CCK(B)/gastrin receptor antagonist and has a long-lasting inhibitory effect on gastric acid secretion.
KW - Acid secretion
KW - CCK(B)
KW - Cat
KW - Gastrin receptor antagonist
KW - Isolated fundic glands
KW - Rabbit
KW - Rat
KW - YM022
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UR - http://www.scopus.com/inward/citedby.url?scp=0031841515&partnerID=8YFLogxK
U2 - 10.1111/j.1472-8206.1998.tb00952.x
DO - 10.1111/j.1472-8206.1998.tb00952.x
M3 - Article
C2 - 9646057
AN - SCOPUS:0031841515
SN - 0767-3981
VL - 12
SP - 256
EP - 262
JO - Fundamental and Clinical Pharmacology
JF - Fundamental and Clinical Pharmacology
IS - 3
ER -