title: Alpha 2-adrenoceptor-blocking properties of midaglizole (DG-5128) in rats.
abstract: The alpha 2-adrenoceptor antagonistic potency of midaglizole was evaluated and compared with that of the selective alpha 2-adrenoceptor antagonists yohimbine and idazoxan. Intravenously administered midaglizole, like yohimbine and idazoxan, reversed the clonidine-induced inhibition of the tachycardic response to cardiac nerve stimulation in pithed rats. Midaglizole, yohimbine and idazoxan inhibited the pressor responses to B-HT 920 (alpha 2-adrenoceptor agonist), in a dose-related manner, to a greater extent than the response to methoxamine (alpha 1-adrenoceptor agonist). Conversely, prazosin produced a highly selective antagonism of the methoxamine-evoked response in this preparation. Midaglizole failed to antagonize centrally mediated hypotension and bradycardia induced by intravenous clonidine, whereas the other alpha 2-antagonists attenuated the clonidine-induced cardiovascular responses in intact rats. These results suggest that midaglizole is a selective alpha 2-adrenoceptor antagonist and, unlike yohimbine and idazoxan, is characterized by its ability to block peripheral but not central alpha 2-adrenoreceptors when administered systemically.
authors.affiliation: Research Institute, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hirohashi
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: I
authors.initials: I
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Akashi
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D001381:Azepines; D007093:Imidazoles; D015016:Yohimbine; C032368:midaglizole; C024763:talipexole; D008729:Methoxamine; D003000:Clonidine