title: The altered disposition of methamphetamine in the model of methamphetamine-induced neurotoxicity.
abstract: Methamphetamine (METH) is a drug of abuse, causing neurotoxic effects in mammals. Many hypotheses have been proposed to explain the underlying mechanisms of METH-induced toxicity, based on neurochemical/neuroanatomical changes. However, the pharmacokinetic properties of METH in the METH-induced neurotoxic model have not yet been evaluated. Thus, we investigated plasma and tissue levels of METH in the METH-induced neurotoxic model. As a result, when METH is administered multiply (5 mg/kg 4 times at 2-h intervals) in male Wistar rats, plasma METH levels at the third and forth injections were significantly higher than those at the first. The tissue distributions of METH in the brain as well as in the kidney were significantly decreased in the third injections, suggesting the importance of decreased transport of METH into tissues. Alternatively, one week after the establishment of METH-induced neurotoxicity, plasma levels of METH were back to normal, although METH levels in brain microdialysates were significantly higher than those in normal animals. These results suggest that the altered pharmacokinetic properties of METH, due to the abnormal membrane transport/disposition of METH into both central and peripheral tissues, might partially affect the emergence of METH-induced neurotoxicity.
authors.affiliation: Department of Medical Technology, Nagoya University Graduate School of Medicine, Nagoya 461-8763, Japan.
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Kitaichi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ito
authors.forename: Masaya
authors.initials: M
authors.lastname: Fukuda
authors.forename: Nagisa
authors.initials: N
authors.lastname: Aoyama
authors.forename: Hironao
authors.initials: H
authors.lastname: Nakayama
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takagi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000097:blood* / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008694:Methamphetamine