PMID- 25335860
OWN - NLM
STAT- MEDLINE
DCOM- 20160202
LR  - 20211021
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 79
IP  - 5
DP  - 2015 May
TI  - Effect of netazepide, a gastrin/CCK2 receptor antagonist, on gastric acid 
      secretion and rabeprazole-induced hypergastrinaemia in healthy subjects.
PG  - 744-55
LID - 10.1111/bcp.12534 [doi]
AB  - AIMS: To compare gastric acid suppression by netazepide, a gastrin/CCK2 receptor 
      antagonist, with that by a proton pump inhibitor (PPI), and to determine if 
      netazepide can prevent the trophic effects of PPI-induced hypergastrinaemia. 
      METHODS: Thirty healthy subjects completed a double-blind, randomized, parallel 
      group trial of oral netazepide and rabeprazole, alone and combined, once daily 
      for 6 weeks. Primary end points were: basal and pentagastrin-stimulated gastric 
      acid and 24 h circulating gastrin and chromogranin A (CgA) at baseline, start and 
      end of treatment, gastric biopsies at baseline and end of treatment and basal and 
      pentagastrin-stimulated gastric acid and dyspepsia questionnaire after treatment 
      withdrawal. RESULTS: All treatments similarly inhibited pentagastrin-stimulated 
      gastric acid secretion. All treatments increased serum gastrin, but the 
      combination and rabeprazole did so more than netazepide alone. The combination 
      also reduced basal acid secretion. Rabeprazole increased plasma CgA, whereas 
      netazepide and the combination reduced it. None of the biopsies showed 
      enterochromaffin-like (ECL) cell hyperplasia. Withdrawal of treatments led 
      neither to rebound hyperacidity nor dyspepsia. CONCLUSIONS: Netazepide suppressed 
      pentagastrin-stimulated gastric acid secretion as effectively as did rabeprazole. 
      The reduction in basal acid secretion and greater increase in serum gastrin by 
      the combination is consistent with more effective acid suppression. Despite our 
      failure to show rabeprazole-induced ECL cell hyperplasia and rebound 
      hyperacidity, the increase in plasma CgA after rabeprazole is consistent with a 
      trophic effect on ECL cells, which netazepide prevented. Thus, netazepide is a 
      potential treatment for the trophic effects of hypergastrinaemia and, with or 
      without a PPI, is a potential treatment for acid-related conditions.
CI  - (c) 2014 The British Pharmacological Society.
FAU - Boyce, Malcolm
AU  - Boyce M
AD  - Hammersmith Medicines Research, Central Middlesex Hospital, London, NW10 7NS, UK.
FAU - Dowen, Sally
AU  - Dowen S
FAU - Turnbull, Gillian
AU  - Turnbull G
FAU - van den Berg, Frans
AU  - van den Berg F
FAU - Zhao, Chun-Mei
AU  - Zhao CM
FAU - Chen, Duan
AU  - Chen D
FAU - Black, James
AU  - Black J
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Benzodiazepinones)
RN  - 0 (Gastrins)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Receptor, Cholecystokinin B)
RN  - 32828355LL (Rabeprazole)
RN  - HOU4I0G29C (YF 476)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Benzodiazepinones/administration & dosage/adverse effects/blood/*pharmacology
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Gastric Acid/*metabolism
MH  - Gastric Mucosa/drug effects/metabolism/ultrastructure
MH  - Gastrins/blood
MH  - Healthy Volunteers
MH  - Humans
MH  - Hyperplasia/chemically induced/prevention & control
MH  - Male
MH  - Middle Aged
MH  - Phenylurea Compounds/administration & dosage/adverse effects/blood/*pharmacology
MH  - Rabeprazole/administration & dosage/adverse effects/blood/*pharmacology
MH  - Receptor, Cholecystokinin B/*antagonists & inhibitors
MH  - *Stomach/drug effects/pathology
MH  - Young Adult
PMC - PMC4415711
OTO - NOTNLM
OT  - chromogranin A
OT  - gastric acid
OT  - gastrin/CCK2 receptor antagonist
OT  - hypergastrinaemia
OT  - netazepide
OT  - rabeprazole
EDAT- 2014/10/23 06:00
MHDA- 2016/02/03 06:00
PMCR- 2016/05/01
CRDT- 2014/10/23 06:00
PHST- 2014/05/14 00:00 [received]
PHST- 2014/10/16 00:00 [accepted]
PHST- 2014/10/23 06:00 [entrez]
PHST- 2014/10/23 06:00 [pubmed]
PHST- 2016/02/03 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - 10.1111/bcp.12534 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2015 May;79(5):744-55. doi: 10.1111/bcp.12534.