A comparison of some of the pharmacological properties of etintidine, a new histamine H2-receptor antagonist, with those of cimetidine, ranitidine and tiotidine.
Etintidine is a competitive antagonist of histamine H2-receptors in the isolated spontaneously beating guinea-pig right atrium with a pA2 value of 6.6 relative to values of 6.2, 6.7 and 7.3 for cimetidine, ranitidine and tiotidine, respectively. Low affinities for histamine H1 (pA2 = 4.2), cholinergic (pA2 = 4.4) and beta adrenergic (pA2 = 3.8) receptors indicated that etintidine has a high degree of specificity for the H2-receptor. The other antagonists studied also exhibited low affinities for these receptors; however, relative to these compounds, etintidine demonstrated a somewhat greater affinity for cholinergic receptors. Etintidine also antagonized basal gastric acid secretion in the conscious gastric fistula rat and histamine, pentagastrin, carbachol, 2-deoxy-D-glucose and meal-stimulated gastric acid secretion in conscious gastric fistula and Heidenhain pouch dogs. After oral administration to conscious Heidenhain pouch dogs, ED50 values for the inhibition of near maximal gastric acid secretion stimulated by histamine were 7.1, 5.4, 0.74 and 0.69 mumol/kg for cimetidine, etintidine, ranitidine and tiotidine, respectively. Onset and duration of the gastric antisecretory activities of the four compounds were similar. The order of potency as histamine H2-receptor and gastric antisecretory antagonists was cimetidine less than etintidine less than ranitidine less than tiotidine. Based on the high degree of specificity for the H2-receptor and its potent gastric antisecretory activity, etintidine may prove to be a useful agent in the treatment of peptic ulcer disease.
D000319:Adrenergic beta-Antagonists; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology / Q000031:analogs & derivatives; D004285:Dogs; D005260:Female; D005663:Furans / Q000494:pharmacology; D005750:Gastric Juice / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010276:Parasympatholytics; D011899:Ranitidine; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D005663:Furans; D006146:Guanidines; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D010276:Parasympatholytics; D013844:Thiazoles; D002927:Cimetidine; D011899:Ranitidine; C036616:etintidine; C023990:tiotidine