Dopamine uptake inhibitors block long-term neurotoxic effects of methamphetamine upon dopaminergic neurons.
A single large dose (100 mg/kg, s.c.) of methamphetamine (MA) is known to exert neurotoxic effects on dopaminergic neurons. The potency at which a series of dopamine (DA) uptake inhibitors blocked MA-induced neostriatal depletions (amfonelic acid (AFA) much greater than mazindol (MAZ) greater than or equal to bupropion (BUP) greater than benztropine (BENZ)) was similar to their potency at blocking 6-hydroxydopamine (6-OHDA) neurotoxicity in rats. Amfonelic acid was able to block long-term neostriatal DA depletions when given 8 h, but not 16 h, after a single large MA dose. These results suggest that an intact and functional DA uptake site is necessary for the development of MA-induced long-term DA depletions.
Marek
G J
GJ
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.
Vosmer
G
G
Seiden
L S
LS
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D006892:Hydroxydopamines / Q000633:toxicity; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008454:Mazindol / Q000494:pharmacology*; D008694:Methamphetamine / Q000633:toxicity*; D009268:Nalidixic Acid / Q000031:analogs & derivatives; D009287:Naphthyridines / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology
D006892:Hydroxydopamines; D007211:Indoles; D009287:Naphthyridines; D009498:Neurotoxins; D014179:Neurotransmitter Uptake Inhibitors; D012701:Serotonin; D009268:Nalidixic Acid; D008694:Methamphetamine; D016627:Oxidopamine; D008454:Mazindol; C006486:amfonelic acid; D004298:Dopamine