title: Inhibition of acid secretion in guinea pigs by tricyclic antidepressants: comparison with ranitidine and omeprazole.
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 micrograms/kg/hr) increased acid and fluid secretion by 3- to 4-fold. When acid output peaked, a bolus administration of the tricyclic anti-depressant 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 mumol/kg), followed by the gastric H-K-adenosine triphosphatase inhibitor, omeprazole (IC50, 0.5-0.6 mumol/kg). Imipramine (IC50 1-2 mumol/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 mumol/kg), an H1 antagonist, and atropine (12 mumol/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.
authors.affiliation: Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: S
authors.initials: S
authors.lastname: Batzri
authors.forename: O
authors.initials: O
authors.lastname: Brugada
authors.forename: J W
authors.initials: JW
authors.lastname: Harmon
authors.forename: N M
authors.initials: NM
authors.lastname: Rich
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D006168:Guinea Pigs; D017506:H(+)-K(+)-Exchanging ATPase; D007099:Imipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D010295:Parietal Cells, Gastric / Q000187:drug effects*; D011398:Promethazine / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology*
chemical_list: D001285:Atropine; D011899:Ranitidine; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D011398:Promethazine; D009853:Omeprazole; D007099:Imipramine