The neurotoxic effects of methylenedioxymethamphetamine (MDMA) and its metabolites on rat brain spheroids in culture.
作者： T.M. Walker , J.E. Davenport-Jones , R.M. Fox , C.K. Atterwill
关键词:
摘要: Rat whole-brain spheroids were used to assess the intrinsic neurotoxicity of methylenedioxymethamphetamine (MDMA, Ecstasy) and two its metabolites, dihydroxymethamphetamine (DHMA) 6-hydroxy-MDMA (6-OH MDMA). Exposure brain MDMA or metabolite 6-OH (up 500 μmol/L) for 5 days in culture did not alter intracellular levels glutathione (GSH), glial fibrillary acidic protein (GFAP) serotonin (5-HT). In contrast, exposure DHMA, which can deplete thiols, significantly increased GSH 170% control) following 50 100 μmol/L DHMA. There was also a significant reduction by DHMA at highest concentration tested (500 but there no effect on 5HT. This may constitute sublethal neurotoxic compensatory response an attempt replenish depleted intraneural exposure. thus be useful vitro model delineate mechanisms effects this class neurotoxin.
springer.com
sci-hub.se 参考文章(20)
M Hiramatsu, A K Cho, Y Kumagai, S E Unger, Metabolism of methylenedioxymethamphetamine: formation of dihydroxymethamphetamine and a quinone identified as its glutathione adduct. Journal of Pharmacology and Experimental Therapeutics. ,vol. 254, pp. 521- 527 ,(1990)
C J Schmidt, Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics. ,vol. 240, pp. 1- 7 ,(1987)
Aron Moscona, Cell suspensions from organ rudiments of chick embryos Experimental Cell Research. ,vol. 3, pp. 535- 539 ,(1952) , 10.1016/0014-4827(52)90077-3
Lena Y. Lin, Yoshito Kumagai, Arthur K. Cho, Enzymatic and chemical demethylenation of (methylenedioxy)amphetamine and (methylenedioxy)methamphetamine by rat brain microsomes. Chemical Research in Toxicology. ,vol. 5, pp. 401- 406 ,(1992) , 10.1021/TX00027A013
G.T. Tucker, M.S. Lennard, S.W. Ellis, H.F. Woods, A.K. Cho, L.Y. Lin, A. Hiratsuka, D.A. Schmitz, T.Y.Y. Chu, The demethylenation of methylenedioxymethamphetamine ("ecstasy") by debrisoquine hydroxylase (CYP2D6). Biochemical Pharmacology. ,vol. 47, pp. 1151- 1156 ,(1994) , 10.1016/0006-2952(94)90386-7
Paul J. Hissin, Russell Hilf, A fluorometric method for determination of oxidized and reduced glutathione in tissues Analytical Biochemistry. ,vol. 74, pp. 214- 226 ,(1976) , 10.1016/0003-2697(76)90326-2
Solomon H. Snyder, Julius Axelrod, Mark Zweig, A sensitive and specific fluorescence assay for tissue serotonin Biochemical Pharmacology. ,vol. 14, pp. 831- 835 ,(1965) , 10.1016/0006-2952(65)90102-4
R.Timothy Miller, Serrine S Lau, Terrence J Monks, 2,5-bis-(Glutathion-S-yl)-α-methyldopamine, a putative metabolite of (±)-3,4-methylenedioxyamphetamine, decreases brain serotonin concentrations European Journal of Pharmacology. ,vol. 323, pp. 173- 180 ,(1997) , 10.1016/S0014-2999(97)00044-7
Joseph W. Vanable, A ninhydrin reaction giving a sensitive quantitative fluorescence assay for 5-hydroxytryptamine Analytical Biochemistry. ,vol. 6, pp. 393- 403 ,(1963) , 10.1016/0003-2697(63)90092-7
Maya Frankfurt, James O'Callaghan, Alain Beaudet, 5,7-Dihydroxytryptamine injections increase glial fibrillary acidic protein in the hypothalamus of adult rats. Brain Research. ,vol. 549, pp. 138- 140 ,(1991) , 10.1016/0006-8993(91)90609-Y