Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/43290
Title: Neuronal nicotinic receptors as new targets foramphetamine-induced oxidative damage and neurotoxicity
Author: Pubill Sánchez, David
Garcia Ratés, Sara
Camarasa García, Jordi
Escubedo Rafa, Elena
Keywords: Èxtasi (Droga)
Receptors nicotínics
Amfetamines
Neurotoxicologia
Ecstasy (Drug)
Nicotinic receptors
Amphetamines
Neurotoxicology
Issue Date: 15-Jun-2011
Publisher: MDPI Publishing
Abstract: Amphetamine derivatives such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are drugs widely abused in a recreational context. This has led to concern because of the evidence that they are neurotoxic in animal models and cognitive impairments have been described in heavy abusers. The main targets of these drugs are plasmalemmal and vesicular monoamine transporters, leading to reverse transport and increased monoamine efflux to the synapse. As far as neurotoxicity is concerned, increased reactive oxygen species (ROS) production seems to be one of the main causes. Recent research has demonstrated that blockade of 7 nicotinic acetylcholine receptors (nAChR) inhibits METH- and MDMA-induced ROS production in striatal synaptosomes which is dependent on calcium and on NO-synthase activation. Moreover, 7 nAChR antagonists (methyllycaconitine and memantine) attenuated in vivo the neurotoxicity induced by METH and MDMA, and memantine prevented the cognitive impairment induced by these drugs. Radioligand binding experiments demonstrated that both drugs have affinity to 7 and heteromeric nAChR, with MDMA showing lower Ki values, while fluorescence calcium experiments indicated that MDMA behaves as a partial agonist on 7 and as an antagonist on heteromeric nAChR. Sustained Ca increase led to calpain and caspase-3 activation. In addition, modulatory effects of MDMA on 7 and heteromeric nAChR populations have been found.
Note: Reproducció del document publicat a: http://dx.doi.org/10.3390/ph4060822
It is part of: Pharmaceuticals, 2011, vol. 4, num. 6, p. 822-847
Related resource: http://dx.doi.org/10.3390/ph4060822
URI: http://hdl.handle.net/2445/43290
ISSN: 1424-8247
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

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