Abstract
1, 1'-Heptamethylene-bis-6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline (HBDT) and 1, 1'-tetramethylene-bis-6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline (bisobrin) produced an edema when given subcutaneously into the hind paws of rats. The inhibitory effects of various antagonists on the paw edema and fibrinolysis induced by HBDT were examined in rats to determine whether chemical mediators other than histamine were involved. The relation of histamine to the fibrinolytic activity of these bis-tetrahydroisoquinoline derivatives has already been reported. Both the edema and fibrinolysis were significantly inhibited by pretreatment with promethazine, cyproheptadine or phentolamine, but not by dibenamine, propranolol, atropine, indomethacin or pyridinolcarbamate. ε-Aminocaproic acid inhibited the fibrinolytic activity completely without any effect on the paw edema. HBDT released 5-hydroxytryptamine (5-HT) along with histamine from rat peritoneal mast cells. However, the amount of released 5-HT was considerably smaller than that of histamine. These results suggested that bis-tetrahydroisoquinolines released both histamine and 5-HT and that these mediators produced paw edema and induced fibrinolysis by enhancement of plasmin production.
