GENERAL PHARMACOLOGY OF CIS-MALONATO[(4R,5R)-4,5-BIS(AMINOMETHYL)-2-ISOPROPYL-1,3-DIOXOLANE]PLAT INUM (II)

Abstract

The general pharmacological properties of cis-malonato-[(4R,5R)-4-5-bis(aminomethyl)-2-isopropyl-1,3-dioxo-lane]platinum(II) (SKI 2053 R, CAS 146665-77-2), a new potential anticancer agent, were investigated in mice, rats, guinea pigs, rabbits, cats and dogs. Intravenous administration of SKI 2053 R had no effect on the central nervous system. SKI 2053 R had no effect on the autonomic nervous system and smooth muscles except that it slightly inhibited the spontaneous motility of isolated rabbit ileum at a concentration of 5 x 10(-5) g/ml. SKI 2053 R did not adversely affect the respiratory-cardiovascular junction, or renal function. SKI 2053 R did not significantly alter the levels of serum glucose, serum free fatty acid and plasma lactate, and did not induce hemolysis. SKI 2053 R did not affect blood coagulation mechanism and liver function. SKI 2053 R did not exhibit anti-inflammatory activity. It was observed that SKI 2053 R increased the formation of hemolytic plaque by spleen cells of sensitized mice at high doses (10 mg/kg and 35 mg/kg). Therefore, it is concluded from these general pharmacological studies that SKI 2053 R at the doses showing antitumor activity does not induce severe adverse effects on the central nervous, autonomic nervous, respiratory-cardiovascular, gastrointestinal, peripheral nervous, and other systems in experimental animals.