[Anti-inflammatory activity of benzo(c) phenanthridine derivatives and possible mechanisms of action (author's transl)].
Of five newly synthesized benzo[c]phenanthridine derivatives tested, the two compounds, BPD-I and BPD-II were found to have potent anti-edematous activity with intraperitoneal administration to S.D. rats. BPD-I showed a marked inhibitory effect against acute inflammation such as induced rat paw edema and leucocyte emigration and protein exudation by means of CMC pouch method and capillary permeability enhancement induced by various phlogists. This compound also inhibited subacute and chronic inflammatory responses such as granuloma formation induced by croton oil or cotton pellet. The anti-inflammatory activities of this compound resembled those of hydrocortisone. The inhibitory effects of carragenan edema and capillary permeability enhancement by ATP were strikingly reduced in adrenalectomized rats suggesting involvement of the hypophysis-adrenal systems. Rat serum corticosterone level and hepatic tyrosine aminotransferase activity (TAT) were then measured after BPD-I injection. The serum corticosterone level was increased and shortly after the elevation of corticosterone, hepatic TAT levels also increased. Thus it is concluded that the corticosterone release from adrenal gland plays a role in the anti-inflammatory action of BPD-I.
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents; D002199:Capillary Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004487:Edema / Q000188:drug therapy; D005122:Exudates and Transudates; D007274:Injections, Intraperitoneal; D007962:Leukocytes / Q000187:drug effects; D008099:Liver / Q000201:enzymology; D008297:Male; D010617:Phenanthridines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D011506:Proteins / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship; D014444:Tyrosine Transaminase / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D010617:Phenanthridines; D011506:Proteins; D014444:Tyrosine Transaminase; D003345:Corticosterone