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  • Title: Pharmacological activities of a novel thienodiazepine derivative as a platelet-activating factor antagonist. Effects on microvascular permeability, hypotension and nephrosis.
    Author: Sakuma Y, Shirato M, Nagaoka J, Obaishi H, Tsunoda H, Katayama S, Ono H, Katayama K.
    Journal: Arzneimittelforschung; 1991 Dec; 41(12):1255-9. PubMed ID: 1815526.
    Abstract:
    The effects of a newly synthesized platelet-activating factor (PAF) antagonist, (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123, CAS 131614-02-3) on microvascular permeability, systemic hypotension and nephrosis were investigated. E-6123 inhibited PAF injection-induced microvascular permeability (edema) in guinea pigs after oral administration at 3 micrograms/kg. The inhibitory effects of E-6123 were very potent compared to those of other PAF antagonists. E-6123 reversed PAF and/or endotoxin injection-induced hypotension in rats after intravenous administration at 3 micrograms/kg. The increase in urinary protein excretion of rats in which nephrosis had been induced by intraperitoneal injection of aminonucleoside was not inhibited by oral administration of E-6123 at 10 mg/kg/d.
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