Comparative pharmacology of histamine H2-receptor antagonists.
There was no significant difference between the concentration-dependent inhibitory effects produced by roxatidine acetate, roxatidine and ranitidine on adenylate cyclase derived from isolated and enriched guinea-pig parietal cells. All the compounds shifted the concentration-response curve of histamine to the right and transformation of this data to Schild-plots produced straight lines with slopes greater than 1 but not significantly different from each other. The pA2 values characterising the potencies were roxatidine acetate 6.85 +/- 0.86, roxatidine 7.14 +/- 0.04, and ranitidine 6.92 +/- 0.01. Histamine-stimulated acid production from isolated guinea-pig parietal cells, measured by the 14C-aminopyrine accumulation technique, was similarly affected by the 3 compounds. Schild-plot slopes of roxatidine acetate and ranitidine were not significantly different from unity and pA2 values were similar to those of the adenylate cyclase inhibition, roxatidine acetate 7.15 +/- 0.09, roxatidine 7.03 +/- 0.02, and ranitidine 6.83 +/- 0.10. In conclusion, roxatidine acetate and its major metabolite roxatidine behave like competitive antagonists with potencies similar to ranitidine on H2-receptors on the guinea-pig parietal cell.
Sewing
K F
KF
Abteilung Allgemeine Pharmakologie, Medizinische Hochschule Hannover.
Beil
W
W
Hannemann
H
H
D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D010880:Piperidines / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000187:drug effects
D006635:Histamine H2 Antagonists; D010880:Piperidines; D011970:Receptors, Histamine H2; D011899:Ranitidine; C053742:roxatidine acetate