Histamine H1- and muscarinic receptor antagonist activity of cimetidine and tiotidine in the guinea pig isolated ileum.

The histamine H2-receptor antagonists cimetidine and tiotidine were compared as antagonists for H1- and muscarinic receptors in the guinea pig isolated ileum. Their interactions with histamine were evaluated on the phasic and tonic components of the histamine response. For carbachol, only the phasic component of the response was monitored. For their interactions with histamine, the type of antagonism, surmountable or nonsurmountable, depended upon the choice of response metameter. Evaluation of the antagonism produced by either tiotidine or cimetidine for histamine concentration-response curves based on the phasic response metameter showed an initial dextral shift with surmountable antagonism. With increasing antagonist concentrations the concentration-response curves were further shifted to the right and the maximum response was depressed. When this antagonism was evaluated for histamine concentration-response curves based on the tonic response metameter, cimetidine produced dextral shifts and nonsurmountable antagonism, and tiotidine exhibited only nonsurmountable antagonist activity. pA2 values for cimetidine antagonism of the phasic and tonic components of the histamine response were 3.2 and 3.7 respectively, and pD'2 values for the phasic and tonic components were 1.8 and 2.3 respectively. The pA2 value for tiotidine antagonism of the phasic component was 3.9 and the pD'2 values for the phasic and tonic components were 2.6 and 3.3 respectively. Cimetidine and tiotidine at concentrations which did not depress the phasic component of the histamine response produced surmountable antagonism to the contractile action of carbachol. The pA2 values for cimetidine and tiotidine antagonism of carbachol were 3.8 and 3.6 respectively.