A comparative study with impromidine (SKF 92676), a potent agonist for histamine H2-receptors

Abstract

Histamine, dimaprit and impromidine caused a relaxation on the isolated cat tracheal muscle contracted by acetylcholine or serotonin. Mepyramine partially inhibited the relaxing effect of histamine without altering that of impromidine and dimaprit. Both impromidine and dimaprit produced a dose-dependent fall in perfusion pressure of the isolated perfused guinea-pig lung while histamine has a pressor effect in this preparation which reversed into a depressor one in the presence of mepyramine. Both dimaprit and impromidine also produced a fall in perfusion pressure and urine flow of the isolated perfused rabbit kidney. A rapid tachyphylaxis developed to the effect of impromidine in the kidney but not to dimaprit. A cross-tachyphylaxis was also observed between impromidine and dimaprit. The agonistic potency of impromidine was found to be very much higher than histamine and dimaprit. Metiamide has a competitive inhibitory effect against impromidine and dimaprit on the isolated perfused lung, kidney and tracheal muscle. It was concluded that impromidine is a very potent pure histamine H2-receptor agonist when compared with histamine and dimaprit on the investigated tissues.

Evidence for and against Heterogeneity in the Histamine H₂-Receptor Population

“…However, there are other data which do not fit in this model: in the isolated working heart of the guinea pig, impromidine had the same efficacy as histamine considering both sinus rate and contractility [64]. The same was ob served with the chronotropic effect of guinea pig atrium [34], Furthermore, impromidine and histamine had the same efficacy in the relaxant effect on cat tracheal muscle con tracted by acetylcholine or 5-hydroxytryptamine [1].…”