Central side effects of pentamethylmelamine: biochemical and behavioural studies.
The central side effects of pentamethylmelamine (PMM), an antitumoral agent, were studied on brain neurotransmitters from the biochemical and behavioural points of view. PMM causes a dose-related reduction in the body temperature and motility of mice. 100 mg/kg of PMM lowers the levels of noradrenaline (NA) and raises 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) in the telencephalon. A similar dose increased striatal levels of dopamine (DA) metabolites, homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC), at earlier times (30 min), reducing their levels at 2 hr. These effects disappear at longer times (4 hr). No changes were observed in the levels of 3-methoxytyramine (3-MT), the extraneuronal metabolite of DA. The serotonin metabolite 5-hydroxyindolacetic acid (5HIAA) was almost not affected. PMM and its metabolites do not displace [3H]-spiroperidol from mouse striatal binding sites. These data show that some of the neurological effects induced by PMM are associated with changes in the metabolism and/or release of brain catecholamines but are not mediated by direct action on DA receptors.
D006585:Altretamine / Q000031:analogs & derivatives / Q000633:toxicity*; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011954:Receptors, Dopamine / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D014227:Triazines / Q000633:toxicity*
D001679:Biogenic Amines; D011954:Receptors, Dopamine; D014227:Triazines; D013134:Spiperone; D006585:Altretamine; C022048:pentamethylmelamine; D004298:Dopamine