Evaluation of the neurotoxic potential of N,N-dimethylamphetamine: an illicit analog of methamphetamine.
The purpose of this study was to evaluate the neurotoxic potential of N,N-dimethylamphetamine (N,N-DMA), a controlled substance analog that has recently appeared on the illicit drug market, and compare it to that of methamphetamine, a structurally related drug with known dopaminergic and serotonergic neurotoxic activity. Like methamphetamine, N,N-DMA induced degeneration of nerve terminals in the mouse striatum, but did not produce cell loss in the pars compacta of the substantia nigra. The dopamine-depleting effects of N,N-DMA were approximately one-eighth of those of methamphetamine. Assessment of N,N-DMA's effects on serotonergic neurons showed that it did not produce a long-lasting depletion of serotonin in either the mouse or rat brain. By contrast, equivalent doses of methamphetamine depleted serotonin in the rat brain by 82%. These results indicate that N,N-DMA, the N-methylated analog of methamphetamine, is considerably less potent than its parent compound both as a dopaminergic and serotonergic neurotoxin, and raise the question of whether or not it may be possible to dissociate the neurotoxic effects of methamphetamine from its reinforcing actions by means of N-methylation. Safety of N,N-DMA in humans remains to be investigated.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
G A
GA
Ricaurte
L E
LE
DeLanney
I
I
Irwin
J M
JM
Witkin
J L
JL
Katz
J W
JW
Langston
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013287:Illicit Drugs / Q000633:toxicity*; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D013287:Illicit Drugs; D012701:Serotonin; D008694:Methamphetamine; C003714:dimethylamphetamine; D004298:Dopamine