Protective actions of nafazatrom in traumatic shock.
3-Methyl-(1-[2-naphthyloxy]-ethyl)-2-pyrazolin-5-one (nafazatrom), a new antithrombotic agent, at doses of 0.5 to 2.0 mg/kg significantly prolonged survival of rats after induction of traumatic shock. Nafazatrom did not exert significant effects on arterial blood pressure in either control or shock animals. However, nafazatrom significantly prevented the plasma accumulation of the lysosomal protease cathepsin D and of the cardiotoxic peptide, myocardial depressant factor (MDF). In addition, nafazatrom (10 microgram/ml) significantly stabilized lysosomal membranes in isolated liver lysosomal suspensions, and inhibited proteolysis in pancreatic homogenates. Thus, nafazatrom exerts significant anti-shock activity which appears to be related to its favorable cellular and metabolic effects.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002402:Cathepsin D; D002403:Cathepsins / Q000097:blood; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008247:Lysosomes / Q000201:enzymology; D009201:Myocardial Depressant Factor / Q000378:metabolism; D011720:Pyrazoles / Q000627:therapeutic use*; D047069:Pyrazolones; D051381:Rats; D011919:Rats, Inbred Strains; D012774:Shock, Traumatic / Q000188:drug therapy*
D005343:Fibrinolytic Agents; D009201:Myocardial Depressant Factor; D011720:Pyrazoles; D047069:Pyrazolones; D002403:Cathepsins; D002402:Cathepsin D; C018845:nafazatrom