General pharmacology of cis-malonato[(4R,5R)-4,5-bis-(aminomethyl)-2-isopropyl-1,3-dioxolane]p latinum(II)

The general pharmacological properties of cis-malonato-[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]p latinum(II) (SKI 2053R, CAS 146665-77-2), a new potential anticancer agent, were investigated in mice, rats, guinea pigs, rabbits, cats and dogs. Intravenous administration of SKI 2053R had no effect on the central nervous system. SKI 2053R 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 2053R did not adversely affect the respiratory-cardiovascular system, gastrointestinal system, neuromuscular junction, or renal function. SKI 2053R did not significantly alter the levels of serum glucose, serum free fatty acid and plasma lactate, and did not induce hemolysis. SKI 2053R did not affect blood coagulation mechanism and liver function. SKI 2053R did not exhibit anti-inflammatory activity. It was observed that SKI 2053R 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 2053R 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.