Dimebon attenuates methamphetamine, but not MPTP, striatal dopamine depletion.
Dimebon is an anti-histamine with central nervous system activity. In this report the effects of dimebon as a neuroprotectant in animal models of Parkinson's disease were tested as assessed in methamphetamine- and MPTP-induced striatal dopaminergic toxicity. Dimebon (1mg/kg) administered at 30 min prior to methamphetamine (40mg/kg) significantly reduced the amount of striatal dopamine depletion in mice, without altering the initial methamphetamine-induced increase in body temperature. In contrast, dimebon at either 1 or 25mg/kg administered at 30 min prior to MPTP (35 mg/kg) was unable to prevent MPTP-induced striatal dopamine loss as determined at 7 days post-methamphetamine/MPTP. These data suggest that dimebon may be exerting a neurotoxin specific neuroprotective effect upon the striatal dopaminergic system and may serve as an important tool for discriminating the mechanistic basis of these two dopaminergic neurotoxins.
Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
Werner J
WJ
Geldenhuys
Altaf S
AS
Darvesh
Dean E
DE
Dluzen
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D007211:Indoles / Q000494:pharmacology*; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL
D007211:Indoles; D008694:Methamphetamine; C010119:latrepirdine; D004298:Dopamine