[Butoctamide enhancement of the antitumor activity of 6-mercaptopurine on Ehrlich solid tumors in mice (author's transl)].

Abstract

Effects of butoctamide (N-(2-ethylhexyl)-3-hydroxybutyramide, L-2) on the antitumor activity of 6-mercaptopurine (6-MP) against Ehrlich solid tumors in mice were investigated. No change was observed in tumor growth after either oral or intraperitoneal administration of butoctamide (100 mg/kg/day X 7). This drug increased the activity of a low dose of 6-MP (2.5 approximately 10 mg/kg/day. i.p., X 7), but did not change the activity of a high dose of 6-MP (40 approximately 80 mg/kg/day, i.p., X 7). The antitumor activity of thioinosine (6-MP riboside) was similarly increased by administration of butoctamide (100 mg/kg/day, i.p., X 7). On the other hand, concomitant administration of butoctamide with cyclophosphamide, methotrexate, mitomycin C or adriamycin had no effect on the activity of these anticancer drugs. In butoctamide (100 mg/kg/day, i.p., X 7)-treated mice, the antitumor activities of a single administration of 6-MP and cyclophosphamide were not increased. Butoctamide stimulated the hypoxanthine-guanine phosphoribosyltransferase activity and inhibited the xanthine oxidase activity of mouse liver, to a certain degree as compared to controls. Butoctamide may promote conversion from 6 MP to thioinosinic acid monophosphate to a biologically active state, rather than to thiouric acid or hypoxanthine which would be inactive.

• Authors: K Sasaki, S Furusawa, G Takayanagi
• Journal: Nihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 77 Issue 2 Pg. 131-9 (Feb 1981) ISSN: 0015-5691 [Print] Japan
• PMID: 6894582 (Publication Type: Journal Article)

Chemical References

• Amides
• Hydroxybutyrates
• Thioinosine
• butoctamide
• Mercaptopurine
• Xanthine Oxidase
• Hypoxanthine Phosphoribosyltransferase

Topics

• Amides
• Animals
• Carcinoma, Ehrlich Tumor (drug therapy)
• Hydroxybutyrates (administration & dosage, pharmacology)
• Hypoxanthine Phosphoribosyltransferase (metabolism)
• Liver (enzymology)
• Male
• Mercaptopurine (administration & dosage, therapeutic use)
• Mice
• Thioinosine (therapeutic use)
• Xanthine Oxidase (metabolism)