N1-[(4-Imidazolyl)-phenyl]-N2-isopropylformamidine (
mifentidine,
DA 4577 is a potent and selective H2 antagonist, representative of a new class of compounds, the imidazolylphenyl-formamidines, characterized by a semi-rigid structural conformation.
Mifentidine appeared to be a specific and competitive antagonist of several
histamine-mediated responses. Thus, in isolated guinea pig atria and ventricles it antagonized
histamine chronotropic and
dimaprit inotropic effects in a competitive manner providing affinity estimates (pA2) of 7.66 and 7.74, respectively.
Mifentidine exerted potent antisecretory effects in: the isolated mouse stomach where it antagonized the
acid promoting activity of
histamine (EC50 3.28 mumol/l) but not that of
bethanechol or db-cAMP (
adenosine 3',5'-monophosphate); the lumen perfused stomach of the anaesthetized rat, inhibiting
histamine (ED50 0.1 mumol/kg i.v.) and
pentagastrin (ED50 0.2 mumol/kg i.v.) stimulated secretion; the pylorus ligated rat (ED50 1.35 mumol/kg i.v.); the
gastric fistula dog, reducing the
secretagogue effect of
pentagastrin (ED50 96 nmol/kg i.v.); the conscious dog equipped with the Heidenhain pouch, where it was effective both following intravenous (ED50 119.7 nmol/kg) and
oral administration (ED50 323.8 nmol/kg) in antagonizing
histamine action.
Mifentidine antisecretory effect, examined in the dog, appeared to last for a significantly longer time than that of
ranitidine.
Mifentidine was free of cardiovascular effects (on aortic blood pressure and heart rate) when administered repeatedly to the conscious dog at doses far above those needed to suppress
acid secretion.