Pyrimido-pyrimidine derivative, RA642, a central pressor agent in cat endotoxin shock

The effects of a pyrimido-pyrimidine derivative, RA642, in endotoxin shock were studied. Blood pressure and preganglionic splanchnic nerve (PSN) activity were measured in alpha-chloralosed cats. Within 30 min of intravenous administration of E. coli endotoxin (1 mg/kg), blood pressure and PSN activity were 68 +/- 8% and 47 +/- 10% of control and by 60 min were depressed by 54 +/- 8% and 42 +/- 8%. RA642 (0.25 mg/kg) injected i.v. 30 min after endotoxin, caused blood pressure to recover significantly to 83 +/- 6% of control within 5 min and be maintained at that level. PSN activity was similarly increased to and maintained at 62 +/- 9% of control. The efficacy of RA642 in reversing the lethal consequences of endotoxin shock were dramatic; all treated animals survived whereas the mortality rate of non-treated animals was 83%. This strongly suggests that the central pressor agent, RA642, may have important therapeutic applications in the management of endotoxin shock.