Action of mifentidine and ranitidine on the isolated rat uterus

The new H2-antagonist mifentidine (compound marked DA 4577) was tested for its inhibitory effect on the relaxation induced by histamine on the rat uterus and was compared with the well known H2-blocker ranitidine. Mifentidine was shown to be more effective than ranitidine (about 10 times). However whereas ranitidine behaved as a "classical" competitive antagonist, mifentidine at concentrations of 10(-7) M, caused a remarkable depression of the maximum response to histamine. This "unsurmountable" antagonism may connected with a tight binding of the compound to the receptor with a consequent low degree of dissociation. Ranitidine, but not mifentidine, at concentrations of 10(-5) M was able to potentiate the stimulatory effect of acetylcholine thus confirming also in the uterus its cholinergic-like effects so far observed mainly in the gastrointestinal tract.