Interaction of antidepressants and neuroleptics with histamine stimulated parietal cell adenylate cyclase and H+ secretion.
The tricyclic antidepressants trimipramine and doxepin, and the neuroleptic agents trifluoperazine and haloperidol were tested for their effect on histamine H2-receptor-mediated adenylate cyclase activity and H+ secretion in guinea-pig parietal cells. All compounds inhibited histamine-stimulated adenylate cyclase and H+ secretion in a concentration-dependent manner. The antisecretory potency was 1-2 orders of magnitude higher than that for adenylate cyclase inhibition. All drugs caused a rightward shift in the concentration-response curves of histamine-induced adenylate cyclase activation with Schild-plot lines having a slope significantly different from unity. Histamine-stimulated H+ secretion was inhibited by the drugs in a noncompetitive fashion. These results demonstrate that antidepressants and neuroleptics interfere noncompetitively with the parietal cell histamine H2-receptor and that this receptor blocking activity is not related to the antisecretory activity of the drugs.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004316:Doxepin / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D006168:Guinea Pigs; D006220:Haloperidol / Q000494:pharmacology; D006633:Histamine Antagonists; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000201:enzymology; D014268:Trifluoperazine / Q000494:pharmacology; D014299:Trimipramine / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D006633:Histamine Antagonists; D004316:Doxepin; D014268:Trifluoperazine; D014299:Trimipramine; D000262:Adenylyl Cyclases; D006220:Haloperidol