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Netazepide, a gastrin/CCK2 receptor antagonist, causes dose-dependent, persistent inhibition of the responses to pentagastrin in healthy subjects.

ABSTRACT: AIMS:To confirm by means of pentagastrin, a synthetic gastrin agonist, that netazepide is a gastrin/CCK2 receptor antagonist in healthy subjects, and that antagonism persists during repeated dosing. METHODS:We did two studies in which we infused pentagastrin (0.6??g?kg(-1) ?h(-1) intravenously), aspirated gastric secretion and measured the volume, pH and H(+) secretion rate of the gastric aspirate. First, we did a double-blind, five-way crossover study (n = 10) to assess the effect of single oral doses of netazepide (1, 5, 25 and 100?mg) and placebo on the response to pentagastrin. Then, we did a single-blind, placebo-controlled study (n = 8) to assess the effect of the first and last oral doses of netazepide (100?mg) twice daily for 13 doses on the response to pentagastrin. RESULTS:Netazepide was well tolerated. After placebo, pentagastrin increased the volume and H(+) secretion rate and reduced the pH of gastric aspirate. Compared with placebo, single doses of netazepide caused dose-dependent inhibition of the pentagastrin response (P < 0.02); netazepide (100?mg) abolished the response. After 13 doses, the reduction in volume and H(+) secretion rate persisted (P < 0.001), but the pH effect was mostly lost. CONCLUSIONS:Netazepide is an orally active, potent, competitive antagonist of human gastrin/CCK2 receptors. Antagonism is dose dependent and persists during repeated dosing, despite tolerance to the effect on pH. Further studies are required to explain that tolerance. Netazepide is a tool to study the physiology and pharmacology of gastrin, and merits studies in patients to assess its potential to treat gastric acid-related conditions and the trophic effects of hypergastrinaemia.

SUBMITTER: Boyce M

PROVIDER: S-EPMC3853528 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Netazepide, a gastrin/CCK2 receptor antagonist, causes dose-dependent, persistent inhibition of the responses to pentagastrin in healthy subjects.

Boyce Malcolm M Warrington Steve S Black James J

British journal of clinical pharmacology 20131101 5

<h4>Aims</h4>To confirm by means of pentagastrin, a synthetic gastrin agonist, that netazepide is a gastrin/CCK2 receptor antagonist in healthy subjects, and that antagonism persists during repeated dosing.<h4>Methods</h4>We did two studies in which we infused pentagastrin (0.6 μg kg(-1) h(-1) intravenously), aspirated gastric secretion and measured the volume, pH and H(+) secretion rate of the gastric aspirate. First, we did a double-blind, five-way crossover study (n = 10) to assess the effec ...[more]

PMID: 23432534

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Dataset Information

Netazepide, a gastrin/CCK2 receptor antagonist, causes dose-dependent, persistent inhibition of the responses to pentagastrin in healthy subjects.

Publications

Netazepide, a gastrin/CCK2 receptor antagonist, causes dose-dependent, persistent inhibition of the responses to pentagastrin in healthy subjects.

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