The cardiac pharmacology of tiotidine (LCL 125, 211): a new histamine H2-receptor antagonist.
The cardiac pharmacology of tiotidine, a potent and specific antagonist of H2-receptors, was studied in isolated Langendorff-perfused guinea-pig hearts. At a concentration of 2.5 x 10(-6) M, tiotidine caused a slight prolongation of the P-R interval, but had no effect on rate, contractility or coronary function. Tiotidine competitively antagonized the positive chronotropic action of histamine with an apparent dissociation constant of 3.0 x 10(-8) M (2.3 x 10(-8)-3.8 x 10(-8) M). Tiotidine abolished H2-mediated increases in contractile force leaving H2-mediated negative inotropic responses unopposed. The actions of histamine at the A-V node, manifested by lengthening of the P-R interval and A-V block, were attenuated by 2.5 x 10(-7) M tiotidine; nevertheless, higher concentrations of the antagonist did not produce additional inhibition of the negative dromotropic response. As a function of concentration, tiotidine reduced the incidence and duration of histamine-induced idioventricular arrhythmias. Based on its high affinity and specificity for the H2-receptor and relative lack of cardio-depressant effects, tiotidine appears to be a useful new drug for investigating the role of histamine in cardiac function and dysfunction.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control; D001283:Atrioventricular Node / Q000187:drug effects; D002927:Cimetidine / Q000031:analogs & derivatives*; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*
D006146:Guanidines; D006635:Histamine H2 Antagonists; D013844:Thiazoles; D002927:Cimetidine; D006632:Histamine; C023990:tiotidine