Anti-shock actions of the pyrimido-pyrimidine derivative, RA-642.

Abstract

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.

• Authors: C E Hock, D J Lefer, A M Lefer
• Journal: Methods and findings in experimental and clinical pharmacology (Methods Find Exp Clin Pharmacol) Vol. 8 Issue 5 Pg. 265-9 (May 1986) ISSN: 0379-0355 [Print] Spain
• PMID: 3724301 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cardiotonic Agents
• Pyrimidines
• RA 642
• Cathepsin D

Topics

• Animals
• Blood Pressure (drug effects)
• Cardiotonic Agents (blood, therapeutic use)
• Cathepsin D (metabolism)
• Cats
• In Vitro Techniques
• Male
• Myocardial Contraction (drug effects)
• Pancreas (enzymology)
• Pyrimidines (blood, therapeutic use)
• Rats
• Rats, Inbred Strains
• Shock, Traumatic (drug therapy, physiopathology)
• Time Factors