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Titolo:
An evaluation of I-ephedrine neurotoxicity with respect to hyperthermia and caudate/putamen microdialysate levels of ephedrine, dopamine, serotonin, and glutamate
Autore:
Bowyer, JF; Newport, GD; Slikker, W; Gough, B; Ferguson, SA; Tor-Agbidye, J;
Indirizzi:
Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA Natl Ctr Toxicol Res Jefferson AR USA 72079 icol, Jefferson, AR 72079 USA
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 1, volume: 55, anno: 2000,
pagine: 133 - 142
SICI:
1096-6080(200005)55:1<133:AEOINW>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; METHAMPHETAMINE-INDUCED NEUROTOXICITY; TYROSINE-HYDROXYLASE ACTIVITY; STRIATAL DOPAMINE; CAUDATE-PUTAMEN; D-AMPHETAMINE; PRECOLUMN DERIVATIZATION; NEURONAL DEGENERATION; BRAIN MICRODIALYSATE; AMINO-ACIDS;
Keywords:
neurotoxicity; microdialysis; ephedrine; striatum; dopamine; serotonin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Bowyer, JF Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA Natl Ctr Toxicol Res HFT-132 Jefferson AR USA 72079 R 72079 USA
Citazione:
J.F. Bowyer et al., "An evaluation of I-ephedrine neurotoxicity with respect to hyperthermia and caudate/putamen microdialysate levels of ephedrine, dopamine, serotonin, and glutamate", TOXICOL SCI, 55(1), 2000, pp. 133-142

Abstract

l-Ephedrine is an active ingredient in several herbal formulations with a mechanism of action similar to amphetamine and methamphetamine. However, its potential to damage dopaminergic terminals in the caudate/putamen (CPu) has yet to be fully evaluated. The studies here used in vivo brain microdialysis experiments to determine the systemic doses and extracellular brain levels of E-ephedrine necessary to produce similar increases in CPu extracellular dopamine and marked hyperthermia that were previously shown necessary for amphetamine-induced neurotoxicity in male Sprague-Dawley rats. At an environmental temperature of 23 degrees C, a single 40 mg/kg intraperitoneal (ip) dose of I-ephedrine produced marked hyperthermia (greater than or equal to 40 degrees C), peak microdialysate ephedrine levels of 7.3 +/- 1.2 mu M, and a 20-fold increase in microdialysate dopamine levels. Twenty-five mg/kg produced a lesser degree of hyperthermia, peak microdialysate ephedrinelevels of 2.6 +/- 0.4 mu M, and a 10-fold increase in dopamine levels. Three doses: of 40 mg/kg given at 3-h intervals or 4 doses of 25 mg/kg I-ephedrine given at 2-h intervals were compared with 4 doses of 5 mg/kg d-amphetamine given at 2-h intervals. Multiple doses of either ephedrine or amphetamine caused severe hyperthermia (greater than or equal to 41.3 degrees C) but striatal tissue levels of dopamine 7 days after dosing were reduced only 25% or less by ephedrine compared to the 75% reductions produced by amphetamine. The increases in CPu microdialysate levels of serotonin produced by either 4 x 25 mg/kg E-ephedrine or 4 x 5 mg/kg d-amphetamine did not significantly differ, but elevation of dopamine levels by d-amphetamine were over 2-fold times the level caused by I-ephedrine. Microdialysate glutamate levels were elevated to the same extent by either 25 mg/kg E-ephedrine or 4 x 5mg/kg d-amphetamine. E-Ephedrine may not be as neurotoxic to dopaminergic terminals as d-amphetamine, because non-lethal doses of I-ephedrine do not sufficiently increase the CPu dopamine levels within nerve terminals or theextracellular space to those necessary for a more pronounced long-term dopamine depletion.

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Documento generato il 19/01/20 alle ore 11:35:00