4-Methylthioamphetamine (MTA) is a phenylisopropylamine derivative whose use has been associated with severe intoxications. MTA is usually regarded as a selective serotonin-releasing agent. Nevertheless, previous data have suggested that its mechanism of action probably involves a catecholaminergic component. As little is known about dopaminergic effects of this drug, in this work the actions of MTA upon the dopamine (DA) transporter (DAT) were studied in vitro, in vivo and in silico. Also, the possible abuse liability of MTA was behaviourally assessed. MTA exhibited an in vitro affinity for the rat DAT in the low micromolar range (6.01 lM) and induced a significant, dose-dependent increase in striatal DA. MTA significantly increased c-Fos-positive cells in striatum and nucleus accumbens, induced conditioned place preference and increased locomotor activity. Docking experiments were performed in a homology model of the DAT. In conclusion, our results show that MTA is able to increase extracellular striatal DA levels and that its administration has rewarding properties. These effects were observed at concentrations or doses that can be relevant to its use in human beings.4-Methylthioamphetamine (MTA) is a phenylisopropylamine derivative originally synthesized and evaluated as an anorectic drug more than 40 years ago [1]. Subsequently, it was demonstrated that MTA is a potent, selective and non-neurotoxic serotonin (5-HT)-releasing agent in vitro [2,3] and in vivo [4], an effect that is mediated via the 5-HT transporter (SERT) [5,6]. MTA gained notoriety in the late 1990s as a street drug commonly known as 'flatliner', and its use has been associated with severe intoxications and several deaths [7][8][9][10]. Even though MTA is usually regarded as a selective serotonergic agent, it also potently inhibits monoamine oxidase-A (MAO-A) [4,11], and both hyperthermia [12] and aortic contraction [13] induced by MTA in rodent models can be blocked by a-adrenergic antagonists. In addition, it has been shown that MTA induces dopamine (DA) release from rat striatal synaptosomes pre-loaded with [ 3
RESUMEN: En este trabajo el autor intenta mostrar la relevancia que le corresponde al principio del doble efecto en el razonamiento práctico general y especialmente en el razonamiento jurídico. Para ello procede del siguiente modo. Primero, estudia la naturaleza del principio como regla para la deliberación moral. Segundo, y con el propósito de ilustrar acerca de las principales situaciones a las que el principio se ha aplicado, ofrece una exposición de su desarrollo histórico. Tercero, presenta los argumentos para justificar la necesidad de acoger el principio del doble efecto, probando que este constituye la única forma no consecuencialista de atribuir responsabilidad por lo efectos de los actos humanos. En cuarto lugar, examina el significado de los requisitos del principio e indica la forma en que ellos deben ser comprendidos. Finalmente, señala algunos ejemplos de diversos ámbitos del Derecho en los que el principio puede ser una útil herramienta para el razonamiento judicial y legislativo. Palabras clave: principio del doble efecto, voluntariedad indirecta, intención, efectos colaterales, responsabilidad moral y jurídica.
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