Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Neurochem
2008 Jun 01;1055:1770-80. doi: 10.1111/j.1471-4159.2008.05272.x.
Show Gene links
Show Anatomy links
N,N-dimethyl-thioamphetamine and methyl-thioamphetamine, two non-neurotoxic substrates of 5-HT transporters, have scant in vitro efficacy for the induction of transporter-mediated 5-HT release and currents.
Gobbi M
,
Funicello M
,
Gerstbrein K
,
Holy M
,
Moya PR
,
Sotomayor R
,
Forray MI
,
Gysling K
,
Paluzzi S
,
Bonanno G
,
Reyes-Parada M
,
Sitte HH
,
Mennini T
.
???displayArticle.abstract???
We studied two non-neurotoxic amphetamine derivatives (methyl-thioamphetamine, MTA and N,N-dimethylMTA, DMMTA) interacting with serotonin (5-HT) transporters (SERTs) with affinities comparable to that of p-Cl-amphetamine (pCA). The rank order for their maximal effects in inducing both [(3)H]5-HT release from rat brain synaptosomes or hSERT-expressing HEK-293 cells, and currents in hSERT-expressing oocytes, was pCA > MTA > or = DMMTA. A correlation between drug-induced release and currents is also strengthened by the similar bell shape of the dose-response curves. Release experiments indicated that MTA and DMMTA are SERT substrates although MTA is taken up by HEK-293 cells with a V(max) 40% lower than pCA. The weak effects of MTA and DMMTA in vitro might therefore be due to their properties as 'partial substrates' on the mechanisms, other than translocation, responsible for currents and/or release. After either local or systemic in vivo administration, MTA and DMMTA release 5-HT in a manner comparable to pCA. These findings confirm that the neurotoxic properties of some amphetamine derivatives are independent of their 5-HT-releasing activity in vivo. It is worth noting that only those amphetamine derivatives with high efficiency in inducing 5-HT release and currents in vitro have neurotoxic properties.
P 18706-B02 Austrian Science Research Fund, P 18706-B02 Austrian Science Fund FWF, P 18706 Austrian Science Fund FWF, FWF_P 18706 Austrian Science Fund FWF
Baumann,
1-(m-chlorophenyl)piperazine (mCPP) dissociates in vivo serotonin release from long-term serotonin depletion in rat brain.
2001, Pubmed
Baumann,
1-(m-chlorophenyl)piperazine (mCPP) dissociates in vivo serotonin release from long-term serotonin depletion in rat brain.
2001,
Pubmed
Crespi,
Carrier-dependent and Ca(2+)-dependent 5-HT and dopamine release induced by (+)-amphetamine, 3,4-methylendioxymethamphetamine, p-chloroamphetamine and (+)-fenfluramine.
1997,
Pubmed
Dinopoulos,
Serotonergic innervation of the mature and developing lateral septum of the rat: a light and electron microscopic immunocytochemical analysis.
1993,
Pubmed
Eriksson,
Effects of mCPP on the extracellular concentrations of serotonin and dopamine in rat brain.
1999,
Pubmed
Fischer,
Chemical release of dopamine from striatal homogenates: evidence for an exchange diffusion model.
1979,
Pubmed
Gerstbrein,
Currents in neurotransmitter transporters.
2006,
Pubmed
Gnegy,
The effect of phosphorylation on amphetamine-mediated outward transport.
2003,
Pubmed
Gobbi,
p-Methylthioamphetamine and 1-(m-chlorophenyl)piperazine, two non-neurotoxic 5-HT releasers in vivo, differ from neurotoxic amphetamine derivatives in their mode of action at 5-HT nerve endings in vitro.
2002,
Pubmed
Gobbi,
Releasing activities of d-fenfluramine and fluoxetine on rat hippocampal synaptosomes preloaded with [3H]serotonin.
1992,
Pubmed
Green,
The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy").
2003,
Pubmed
Hoyer,
Partial agonists, full agonists, antagonists: dilemmas of definition.
1993,
Pubmed
Huang,
p-methylthioamphetamine is a potent new non-neurotoxic serotonin-releasing agent.
1992,
Pubmed
Hurtado-Guzmán,
Monoamine oxidase inhibitory properties of optical isomers and N-substituted derivatives of 4-methylthioamphetamine.
2003,
Pubmed
Iyer,
Tryptophan pretreatment augmentation of p-chloroamphetamine-induced serotonin and dopamine release and reduction of long-term neurotoxicity.
1994,
Pubmed
Jensen,
Pharmacological characterization of human excitatory amino acid transporters EAAT1, EAAT2 and EAAT3 in a fluorescence-based membrane potential assay.
2004,
Pubmed
Johnson,
[3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues.
1991,
Pubmed
Johnson,
Combined administration of a non-neurotoxic 3,4-methylenedioxymethamphetamine analogue with amphetamine produces serotonin neurotoxicity in rats.
1991,
Pubmed
Kantor,
Protein kinase C and intracellular calcium are required for amphetamine-mediated dopamine release via the norepinephrine transporter in undifferentiated PC12 cells.
2001,
Pubmed
Khoshbouei,
N-terminal phosphorylation of the dopamine transporter is required for amphetamine-induced efflux.
2004,
Pubmed
Levi,
Carrier-mediated release of neurotransmitters.
1993,
Pubmed
Mager,
Conducting states of a mammalian serotonin transporter.
1994,
Pubmed
,
Xenbase
Mamounas,
Evidence for dual serotonergic projections to neocortex: axons from the dorsal and median raphe nuclei are differentially vulnerable to the neurotoxin p-chloroamphetamine (PCA).
1988,
Pubmed
Meinild,
Zinc potentiates an uncoupled anion conductance associated with the dopamine transporter.
2004,
Pubmed
,
Xenbase
Mennini,
In vitro and in vivo effects of the anorectic agent dexfenfluramine on the central serotoninergic neuronal systems of non-human primates. A comparison with the rat.
1996,
Pubmed
Molliver,
Anatomic evidence for a neurotoxic effect of (+/-)-fenfluramine upon serotonergic projections in the rat.
1990,
Pubmed
Muchimapura,
Isolation rearing in the rat disrupts the hippocampal response to stress.
2002,
Pubmed
Pettibone,
Serotonin-releasing effects of substituted piperazines in vitro.
1984,
Pubmed
Pifl,
Zn2+ modulates currents generated by the dopamine transporter: parallel effects on amphetamine-induced charge transfer and release.
2004,
Pubmed
Raiteri,
A simple apparatus for studying the release of neurotransmitters from synaptosomes.
1974,
Pubmed
Rudnick,
p-Chloroamphetamine induces serotonin release through serotonin transporters.
1992,
Pubmed
Rudnick,
Non-neurotoxic amphetamine derivatives release serotonin through serotonin transporters.
1993,
Pubmed
Scholze,
The role of zinc ions in reverse transport mediated by monoamine transporters.
2002,
Pubmed
Scholze,
Transporter-mediated release: a superfusion study on human embryonic kidney cells stably expressing the human serotonin transporter.
2000,
Pubmed
Scorza,
Effects of 5-HT-releasing agents on the extracellullar hippocampal 5-HT of rats. Implications for the development of novel antidepressants with a short onset of action.
1999,
Pubmed
Seidel,
Amphetamines take two to tango: an oligomer-based counter-transport model of neurotransmitter transport explores the amphetamine action.
2005,
Pubmed
Shankaran,
Involvement of the serotonin transporter in the formation of hydroxyl radicals induced by 3,4-methylenedioxymethamphetamine.
1999,
Pubmed
Shankaran,
Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT.
2001,
Pubmed
Sheehan,
Regulation of affect by the lateral septum: implications for neuropsychiatry.
2004,
Pubmed
Sitte,
Sodium-dependent neurotransmitter transporters: oligomerization as a determinant of transporter function and trafficking.
2004,
Pubmed
Sotomayor,
Acute morphine administration increases extracellular DA levels in the rat lateral septum by decreasing the GABAergic inhibitory tone in the ventral tegmental area.
2005,
Pubmed
Sprague,
An integrated hypothesis for the serotonergic axonal loss induced by 3,4-methylenedioxymethamphetamine.
1998,
Pubmed
