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.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects*
D006635:Histamine H2 Antagonists; D007093:Imidazoles; C039796:mifentidine; D006632:Histamine; D011899:Ranitidine; D000109:Acetylcholine