GENERAL PHARMACOLOGICAL STUDIES ON PEPLEOMYCIN SULFATE (NK 631)

Abstract

Pharmacological actions of pepleomycin sulfate (NK 631) which is a new antitumor agent derived from bleomycin were studied and the following results were obtained.
NK 631 had no significant influences on the central, motor and sensory nervous systems at relatively higher doses (5s 10 i.v., i.p., s.c.). NK 631 (5-40 mg/kg, i.v.) caused a slight decrease in blood pressure in anesthetized rats and slight increases in blood pressure, heart rate and peripheral blood flow in anesthetized dogs.
NK 631 (1-4 mg) given close-arterially caused a slight increase in the developing tension in the isolated blood-perfused papillary muscle. NK 631 slightly contracted the isolated guinea pig ileum and rat uterus but did not affect the contraction of isolated guinea pig trachea. NK 631 caused significant increases in urine output and Cl excretion in saline loaded rats at 20 mg/kg, i.p. By the local injection of NK 631, a slight edema of rat paw and an increase in rabbit cutaneous permeability were observed.
The intraperitoneal injection of NK 631 caused a significant increase in leakage of dye injected intravenously into the peritoneal cavity of mice. NK 631 did not affect hemolysis and prothrombin time at 10^-4g/ml.
In pharmacological actions, significant differences between NK 631 and pepleomycin were not observed.