Gastric and cardiac H-2 receptor effects of dimaprit and N'(Me),5(Me)histamine in conscious dogs.
Two new H-2 agonists 5,N'-dimethyl histamine (DMH), an imidazole analog, and dimaprit, a non-imidazole compound, and histamine (H), a mixed H-1, H-2 agonist, were given to four conscious gastric fistula dogs. Gastric acid was stimulated dose responsively. Dimaprit stimulated a 20% greater maximum output of acid, and more pepsin than the other agents, but inhibited pepsin secretion as doses of greater than 0.63 mumol/kg-h. Heart rate was increased dose responsively by all drugs to approximately 200 beats/min with ED50 of 0.17:0.42:0.80 mumol/kg-h (H:DMH:dimaprit). Normalized dose responses showed that histamine was equipotent on acid and heart rate (ED50 0.15 vs. 0.14 respectively) while DMH (ED50 0.21 vs. 0.40) and dimaprit (ED50 0.27 vs. 0.85) stimulated heart rate less effectively than acid. Histamine was more effective at reducing blood pressure, with approximate ED50 of 0.28:0.60:0.96 for H, DMH and dimaprit respectively. The results indicate considerable heterogeneity of histamine responses for different actions mediated by the H-2 receptors, as well as differences for any one action between H-2 agonists.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D017259:Dimaprit; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005750:Gastric Juice / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007700:Kinetics; D008761:Methylhistamines / Q000494:pharmacology*; D010434:Pepsin A / Q000378:metabolism; D011968:Receptors, Histamine / Q000187:drug effects*; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects*; D013890:Thiourea / Q000494:pharmacology*
D008761:Methylhistamines; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; C024317:5,N'-dimethylhistamine; D010434:Pepsin A; D013890:Thiourea; D017259:Dimaprit