Pharmacological Studies on 3-Formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), a Novel Antiinflammatory Agent. 3rd Communication : The Involvement of Bradykinin in Its Analgesic Actions

概要

論文の詳細を見る
In order to elucidate the analgesic mechanism of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), its effects on the kinin-forming system were examined both in vivo and in vitro. T-614,at doses more than 10 mg/kg p.o., exhibited a significant inhibitory effect on the increased levels of bradykinin released into the pouch fluid of kaolin-induced inflammation in rats. In the kaolin-induced writhing response in mice, which is shown to be mainly dependent on the action of bradykinin, T-614 reduced not only the writhing frequency but also the peritoneal levels of bradykinin in a dose-dependent manner. Whereas, in the zymosan-induced writhing response in which prostaglandin I_2 (PGI_2) is shown to be an important mediator, it did not exert an obvious inhibition on either writhing responses or peritoneal PGI_2 levels at a highest dose of 100 mg/kg. T-614 did not inhibit the activities of serine proteases, such as trypsin, thrombin, kallikrein and plasmin. Furthermore, it did not affect the kinin-forming enzymes of rat plasma in vitro. The above results suggest that the analgesic effects of T-614 may be partly mediated by the inhibition of bradykinin release in the local inflamed tissue.
公益社団法人日本薬学会の論文