title: Interaction between dilazep and alpha-adrenoceptors.
abstract: Dilazep, 1,4-bis-[3-(3,4,5-trimethoxybenzoyl-oxy)propyl]perhydro-1,4-diazep ine, is a novel antianginal agent with an unusual chemical structure. The drug is a weak calcium antagonist. In pithed rats dilazep (10-100 mg/kg i.v.) caused a transient hypotensive effect which was accompanied by a strong and persistent reduction in heart rate. Similarly as observed for other, more potent calcium antagonists dilazep (10-100 mg/kg) counteracted the vasoconstriction, evoked by the stimulation of postsynaptic alpha 2-adrenoceptors with the selective agonist B-HT 920. The antagonism proved noncompetitive. The vasoconstriction, induced upon selective stimulation of postsynaptic alpha 1-adrenoceptors with methoxamine, however, was hardly influenced by dilazep. These findings are in accordance with the calcium-antagonistic activity of dilazep, demonstrable at relatively high doses. From radioligand-binding studies it was concluded that dilazep is an extremely weak antagonist of alpha 1-adrenoceptors, whereas it does not possess any measurable affinity towards alpha 2-adrenoceptors. It seems unlikely that the antianginal activity of dilazep can be fully explained by its weak calcium-antagonistic potency. However, the bradycardic effect of dilazep is probably relevant to its antianginal activity.
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004109:Dilazep / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D001381:Azepines; D011942:Receptors, Adrenergic, alpha; C024763:talipexole; D014700:Verapamil; D004109:Dilazep; D008729:Methoxamine