Histamine receptor blocking effects of cimetidine in the airways.
We investigated the modification of histamine-induced bronchoconstriction by the H2-antagonist cimetidine in conscious sheep. One hundred breaths of 5% histamine aerosol increased mean (SD) pulmonary resistance (RL) by 5.6 (1.4) cmH2O/l/sec. This increase in RL was completely blocked by intravenous clemastine (0.5 mg), a specific H1-antagonist, indicating that the histamine-induced bronchoconstriction was mediated by H1-receptors. Intravenous cimetidine caused a dose-dependent enhancement of the histamine response between 1 and 1000 mg with a mean peak delta RL of 15.3 (5) cmH2O/l/sec (p less than 0.05) at the 1000 mg dose, while it blocked the histamine response at a dose of 2400 mg [delta RL = 1.9 (2) cmH2O/l/sec, p = NS]. This paradoxic effect was not related to an anticholinergic mechanism as intravenous cimetidine (2400 mg) failed to block carbachol-induced (25 breaths of 1% solution) bronchoconstriction. We conclude that in the ovine airway, cimetidine is a selective H2-histamine receptor blocker at lower tissue concentrations, and a combined H2- and H1-histamine receptor blocker at high tissue concentrations.
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology*; D002974:Clemastine / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists; D007275:Injections, Intravenous; D012137:Respiratory System / Q000187:drug effects*; D012756:Sheep
D006146:Guanidines; D006635:Histamine H2 Antagonists; D002927:Cimetidine; D006632:Histamine; D002217:Carbachol; D002974:Clemastine