Inhibition of acid secretion in guinea pigs by tricyclic antidepressants: Comparison with ranitidine and omeprazole

S. Batzri, O. Brugada, J. W. Harmon, N. M. Rich

Research output: Contribution to journalArticlepeer-review

Abstract

The antisecretory properties of imipramine on gastric secretion in guinea pig in comparison with other antisecretory agents was determined. In awake guinea pigs s.c. infusion of histamine (30 μg/kg/hr) increased acid and fluid secretion by 3- to 4-fold. When acid output peaked, a bolus administration of the tricyclic antidepressant imipramine inhibited acid and fluid secretion. Imipramine and other agents, such as ranitidine and omeprazole inhibited gastric secretion in a dose-dependent fashion. The most potent was the H2-antagonist ranitidine (IC50, 0.2-0.3 μmol/kg), followed by the gastric H-K-adenosine triphosphatase inhibitor, omeprazole (IC50, 0.5-0.6 μmol/kg). Imipramine (IC50 1-2 μmol/kg) was the least potent of the inhibitors. Both ranitidine and omeprazole could abolish acid secretion, but maximal inhibition with imipramine was 60% of initial. Promethazine (25 μmol/kg), an H1 antagonist, and atropine (12 μmol/kg), a muscarinic antagonist, inhibited gastric secretion by 40 to 50%. Imipramine and atropine also inhibited basal acid secretion. In dispersed gastric cells comparison between imipramine and omeprazole showed that imipramine was about 5-fold more potent than omeprazole in blocking histamine or dibutyryl cyclic AMP stimulation of aminopyrine accumulation. Imipramine probably acts as a protonophore by increasing the rate of proton-gradient dissipation rather than by interfering with the hydrogen-pump system because, in gastric membranes, imipramine was 20-fold less potent than omeprazole in inhibiting the gastric H-K-adenosine triphosphatase activity. These results suggest that imipramine administered s.c. in guinea pigs is a potent antisecretory drug. Its action may be due to a combination of anticholinergic and antihistamine H2 activities.

Original languageEnglish (US)
Pages (from-to)493-499
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume246
Issue number2
StatePublished - Jan 1 1988
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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