Yes, was ff zoeken maar volgensmij was het dit artikel. V
Ah kijk aan, thanks.
Maar dan staat dit:
Houdt er wel rekening mee dat methylone net zo neurotoxisch is als mdma
Toch haaks op dit:
In de conclusie is te lezen dat de Methylone minder metaboliete interactie vertoont waardoor deze als minder neurotoxisch wordt beschouwd. Daarnaast lijkt het erop dat methylone minder invloed heeft op de DA receptoren.
Een suggestie uit veel literatuur is inderdaad dat de metabolieten van MDMA, in ieder geval deels, verantwoordelijk zijn voor de schade. Dat zie je bij Methylone dus niet terug, omdat niet dezelfde metabolieten worden gevormd, door het kleine maar op dat vlak significante verschil in structuur van MDMA en bk-MDMA.
In ieder geval, fijn dat je het gevonden hebt.
Staan wel interessante zaken voor de geïnteresseerde lezer in het artikel, wat picks:
As with MDMA, it might affect the DA or 5-HT system differently, depending on the animal species used for the experiment. Most authors described the maximum neurotoxic effects of methamphetamine three days after treatment (Pu and Vorhees, 1993) and those of MDMA seven days after treatment(Battaglia et al., 1988). Thus, we examined the neurotoxic injury induced by methylone at 3 and 7 days after following the end of the treatment. In addition, a close relationship was already established between the hyperthermic response and the severity of the brain lesion induced by amphetamines (Sánchez et al., 2004), supporting the hypothesis that MDMA is neurotoxic when a binge dosing schedule is employed and the animals are in a hot environment. Accordingly, present experiments were carried out at a high ambient temperature simulating hot conditions found in dance clubs. We administered the drug at 3-3.5h interval, in accordance with our previous paper characterizing the pharmacokinetics of methylone, distinguished by its short half-life (López-Arnau et al., 2013). To model recreational methylone use, we simulated the widespread practices of “stacking” (taking multiple doses at once in order to increase the desired effect and/or offset tolerance from prior use) and “boosting” (taking supplemental doses over time in order to maintain the drug’s effect). Thus, we chose to administer multiple doses/day of methylone during each treatment.
Overall, our data demonstrate a slight serotonergic toxicity of methylone, one week after treatment, only when four doses are administered in a day.
Following the two treatments performed in this study, methylone induced a transient loss of the DA transporter in the frontal cortex. The initial decline and later recovery of DA transporter points to a biochemical down-regulation in the absence of tissue damagebut we can also assume that a methylone-induced dopamine transporter structural modification could occur, explaining the reduction in binding experiment. This hypothesis is in agreement with our previous results, which demonstrate that methylone inhibits [3H]DA uptake after drug withdrawal, pointing to alterations in the transporter that are more complex than a simple blocking of the carrier (López-Arnau et al., 2013). Unlike MDMA (Chipana et al., 2006), methylone did not alter DA transporter radioligand binding or TH levels in striatum in any of the performed treatments. The main difference between treatments was found in 5-HT terminal markers. When exposure to methylone was performed over two consecutive days with three doses per day, we registered a transient reduction of these markers, but when treatment consisted of four doses in a single day, a more persistent effect appeared, affecting frontal cortex and hippocampus.
Only one study has been published concerning the neurotoxic effect of methylone in DA and 5-HT systems in mice (Hollander et al., 2013). Authors demonstrated that methylone exposure (30 mg/kg, twice daily for 4 days) had no effect on neurotransmitter levels in C57BL/J6 mice two weeks after treatment. Our results demonstrate that methylone neurotoxicity in mice depends on the number of doses and intervals between each dose, as occurs with other cathinones. Furthermore, we suspect that the high room temperature, used in this study, could play an important role in methylone-induced neurotoxicity if we compare our findings with those of Hollander et al. (2013). Nonetheless, further research is necessary in order to assess whether the role of hyperthermia and room temperature is complementary or essential in the advent of methylone-induced neurotoxicity.
Mice differ from other animal species because they display deficits in DA neurotransmission greater than 5-HT after binge MDMA exposure. Present results demonstrated that methylone acts on contrary. The methylone neurochemical profile could be explained by the fact that this drug acts preferentially as an inhibitor for the 5-HT transporter than for the DA transporter (Baumann et al., 2012; López-Arnau et al., 2012; Sogawa et al., 2011), implying a better access of this drug to the 5-HT nerve terminals leading to the corresponding injury. Moreover, a well-recognized hypothesis of MDMA neurotoxicity involves some metabolite participation that has not been demonstrated for methylone.
The impairment induced by methylone on 5-HT and DA terminals is limited to frontal cortex and hippocampus when exposure is clustered in four doses in a day. This mild cathinone neurotoxicitycorrelates with results of our in vitro studies in cortical cultured cells, where we describe that methylone did not show concentration- and time-dependent deleterious effect on neuronal viability. The data reveal that doses up to 1000 µM for 24 to 48 h do not appreciably affect cell viability. This is a remarkable finding, which confirms previous studies that found methylone alone is not cytotoxic even at high doses (Nakagawa et al., 2009; Sogawa et al., 2011). In this regard, other studies assessing the effects of MDMA on cortical or hippocampal cultured cell viability reported no or low cell death following exposure to high MDMA concentrations(Capela et al., 2006). [ ---> Deze studie beschrijft idd dat MDMA zelf weinig tot geen schade geeft aan cellen op "culture" ; wat onderstreept dat de metabolieten die zich in het lichaam wél vormen, maar in celcultuur niet (bij gebrek aan een lever in een celmodel van cortex en hippocampus..) de schade berokkenen.
In conclusion, our results demonstrate that methylone-induced brain consequences differ according to treatment schedule (dose, number of doses and dose interval). Neurochemical changes elicited by methylone are apparent when administered at an elevated ambient temperature, four times per day at 3h intervals. This schedule is related with patterns used by humans and agree with methylone’s half-life in rodents (López-Arnau et al., 2013). Following this, we found decrease in frontal cortex and hippocampal serotoninergic nerve ending markers around 20-25% together with hippocampal astrogliosis suggesting nerve ending injuries. No effect in striatum was evidenced. Methylone did not show a cytotoxic effect in cortical cultured neurons. The limited neurotoxicity found in this study, however, should not preclude advice concerning the high risk of acute fatal effects affecting the cardiovascular system and thermoregulation.
Aantal zaken om er uit te halen, mits je veronderstelt dat onderzoek in de muis zich vertaald naar de mens (wat niet perse zo is, maar waarvan je ook niet kunt zeggen dat het volslagen onzin is...kortom de waarheid ligt daar in het midden); 1) letten op je temperatuur 2) niet binge dosen, bij voorkeur wellicht 3-4 dosissen per dag vermijden. 3) de eventuele veranderingen zijn zichtbaar afhankelijk van dosis, aantal dosissen en tijdsinterval en worden daarbij zichtbaar bij 4x/dag toediening in een warme omgeving bij de muis.
De vraag is natuurlijk in hoeverre zich e.a. vertaald naar de mens; maar better safe than sorry..dus een aantal key elements er wel uithalen en smelten in je eigen model van verantwoord gebruik
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