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Comparative pharmacology of penta methyl melamine and hexa methyl melamine in mice



Comparative pharmacology of penta methyl melamine and hexa methyl melamine in mice



Cancer Research 40(8 PART 1): 2762-2767



The comparative pharmacology of pentamethylmelamine (PMM) and hexamethylmelamine (HMM) [an antineoplastic drug] was determined in mice. PMM administered i.p. at 1/10 of a lethal dose (175 mg/kg) produced a maximum 18% reduction in the peripheral white blood cell count of normal mice. This same dose of PMM produced 70% inhibition of DNA synthesis in Lieberman [mouse] plasmacytoma ascites cells 48 h after drug administration. HMM administered i.p. at 1/10 of a lethal dose (200 mg/kg) inhibited Lieberman plasmacytoma DNA synthesis by 80% at 48 h. The time course of tumor cell RNA synthesis inhibition was comparable for the 2 drugs, with a maximum 60% inhibition at 8 h postinjection and recovery to only 20-30% inhibition at 72 h. The pharmacological disposition of PMM in mice was compared to HMM after i.p. administration of 1/10 of a lethal dose of ring-14C-labeled drug. Concentration of intact drug in plasma and tissues was determined by high-pressure liquid chromatography. HMM and PMM disappeared rapidly from the plasma with a half-life of .apprx. 40 min. In contrast to these results with intact drug, the peak plasma level of radiolabel was attained at 1 h after administration for both compounds. The highest tissue concentrations of [ring-14C]PMM or HMM were found in the liver and small intestine. Despite the increased water solubility of PMM, the peak concentration of radiolabel in the brain at 4 min after injection was 3-fold higher than that attained with HMM, and the maximum concentration of PMM in the brain after PMM was 14-fold higher than that attained after HMM. Neurotoxicity, including flaccid paralysis, was observed in the mice within 15 min after PMM administration, and continued for 4-5 h.

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Accession: 004997525

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PMID: 6771004



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