Human central nervous system pharmacology of pentamethylmelamine and its metabolites.
Pentamethylmelamine (PMM) 80 mg/m2 was administered I.V. to 8 patients during surgical resection of intracerebral tumors. PMM concentrations in tumors were generally much higher than concurrent plasma concentrations, ranging from undetectable (less than .01 micrograms/g) to as high as 4.47 micrograms/g and were much higher in malignant melanoma samples than in astrocytoma samples. PMM was barely detectable or undetectable in most samples of edematous brain tissue adjacent to intracerebral tumor and in temporalis muscle. The PMM metabolites tetramethylmelamine (TeMM), trimethylmelamine (TrMM), and dimethylmelamine (DMM) were each detectable in tumor samples from one or two patients. Monomethylmelamine (MMM) was present in tumor samples from all except one patient. MMM was noted in samples of edematous brain tissue adjacent to tumor from 4 of 8 patients. It was the only PMM metabolite found in brain. TrMM, DMM, and MMM but not PMM, and TeMM were found in tumor cyst fluid from a patient with an intracerebral malignant melanoma. Two patients receiving therapeutic doses of PMM had biopsies taken of subcutaneous malignant melanoma deposits. PMM was undetectable in samples from one patient but reached high concentrations in the other patient. In both patients, MMM was the major metabolite. There was no indication that PMM penetrated into extracerebral tumors more readily than into intracerebral tumors Cerebrospinal fluid (CSF) samples were obtained from one patient without neurological toxicity who received low doses of PMM and from 4 patients receiving high doses of PMM who had developed neurological toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
D006585:Altretamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D014227:Triazines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D014227:Triazines; D006585:Altretamine; C022048:pentamethylmelamine