Histamine H2-receptor antagonism by propantheline and derivatives.
The histamine H2-antagonist properties of propantheline and its tertiary amine derivatives were investigated. Propantheline and methantheline inhibited the histamine-activated cyclase of guinea-pig brain homogenates, a well characterized H2-receptor preparation; the inhibition was not competitive. Tertiary amine derivatives were competitive H2-antagonist in this system, one such derivative exhibiting greater potency than cimetidine. In concentrations blocking the brain H2-receptors, these derivatives had no effect on atrial histamine dose-response curves, but evidence for their antagonism on peripheral H2-receptors was obtained with papillary muscle preparations. The results suggest that the guinea-pig brain H2-linked cyclase of homogenates is a sensitive predictor of peripheral H2-antagonist activity. These drugs may also be effective inhibitors of gastric secretion.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006624:Hippocampus / Q000201:enzymology; D006635:Histamine H2 Antagonists; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011413:Propantheline / Q000031:analogs & derivatives* / Q000494:pharmacology*
D006635:Histamine H2 Antagonists; D011413:Propantheline; D000262:Adenylyl Cyclases