Effect of Dilazep on the Automaticity of Rat Isolated Heart

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The effect of Dilazep (1, 4-bis [3, 4, 5-trimethoxybenzoyloxy) propyl] perhydro-1, 4-diazepine dihydrochloride monohydrate)on the automaticity of rat isolated heart in erythrocyte suspension and whole blood was studied. The effect of Dilazep was compared with Dipyridamole, Propranolol, o-lodo Sodium Benzoate (OISB) and the metabolites of Dilazep (Monoester-type, Trimethoxybenzoic acid and bis-Hydroxypropyl perhydro-1, 4-diazepine). Although Dilazep prolonged the automaticity with the concentration more than 3×10<SUP>-6</SUP>M in vitro, or after 0.3mg/kg i.v. or 300mg/kg p.o. administration, Dipyridamole, Propranolol, and OISB showed no prolongation. On the contrary, Propranolol and OISB suppressed the automaticity in high concentration. Among the metaboiltes of Dilazep, only monoester-type prolonged the automaticity, and it's intensity corresponded to about 1/100 as that of Dilazep.<BR>Although it has not been clear the action mechanism of Dilazep on the automaticity, it is considered Dilazep would act through erythrocyte, because it's effect was seen in whole blood or erythrocyte suspension.
Japan Society of Clinical Chemistryの論文