TY - JOUR
T1 - Evaluation of the neurotoxic potential of N,N-dimethylamphetamine
T2 - an illicit analog of methamphetamine
AU - Ricaurte, G. A.
AU - DeLanney, L. E.
AU - Irwin, I.
AU - Witkin, J. M.
AU - Katz, J. L.
AU - Langston, J. W.
PY - 1989/6/26
Y1 - 1989/6/26
N2 - 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.
AB - 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.
KW - Dopamine
KW - Drug abuse
KW - Methamphetamine
KW - Neurotoxicity
KW - Serotonin
UR - http://www.scopus.com/inward/record.url?scp=0024348380&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024348380&partnerID=8YFLogxK
U2 - 10.1016/0006-8993(89)90247-3
DO - 10.1016/0006-8993(89)90247-3
M3 - Article
C2 - 2765865
AN - SCOPUS:0024348380
SN - 0006-8993
VL - 490
SP - 301
EP - 306
JO - Brain research
JF - Brain research
IS - 2
ER -