Anti-shock actions of the pyrimido-pyrimidine derivative, RA-642.
The anti-shock actions of RA-642 were studied in traumatic shock in rats. The shock state was characterized by a significantly reduced mean arterial blood pressure (MABP), a five-fold increase in plasma cathepsin D activity, a three-fold increase in plasma myocardial depressant factor (MDF) activity, and a mean survival time of 1.6 +/- 0.3 h. Administration of 0.5 mg/kg of the pyrimido-pyrimidine derivative, RA-642, significantly prolonged survival time to 3.7 +/- 0.6 h (p less than 0.01). Plasma cathepsin D activity was not affected by RA-642 although accumulation of the cardiotoxic peptide MDF was significantly blunted (p less than 0.025). This effect on MDF accumulation may be related to the potent antiproteolytic action of RA-642 in vitro. Results indicate that RA-642 provides significant beneficial effects in a severe model of traumatic shock.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000097:blood / Q000627:therapeutic use*; D002402:Cathepsin D / Q000378:metabolism; D002415:Cats; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010179:Pancreas / Q000201:enzymology; D011743:Pyrimidines / Q000097:blood / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012774:Shock, Traumatic / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
D002316:Cardiotonic Agents; D011743:Pyrimidines; C010650:RA 642; D002402:Cathepsin D