Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/21373
Title: Involvement of nicotinic receptors in methamphetamine and MDMA induced neurotoxicity: Pharmacological studies
Author: Escubedo Rafa, Elena
Garcia Ratés, Sara
Camarasa García, Jordi
Pubill Sánchez, David
Keywords: Receptors nicotínics
Amfetamines
Nicotinic receptors
Amphetamines
Issue Date: 2011
Publisher: Transworld Research Network
Abstract: During the last years, our emphasis has focused in the study of the neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) on central nervous system and their pharmacological prevention. In the process of this research, we have used a semipurified synaptosomal preparation from striatum of mice or rats as a reliable in vitro model to study reactive oxygen species (ROS) production by these amphetamine derivatives, which is well correlated with their dopaminergic injury in in vivo models. Using this preparation we have demonstrated that blockade of alpha7 nicotinic receptors with methyllycaconitine (MLA) and memantine (MEM) prevents ROS production induced by MDMA and METH. Studies at molecular level showed that both, MDMA and METH, displaced competitively the binding of radioligands for homomeric alpha7 and heteromeric nAChRs, indicating that they can directly interact with them. In all the cases MDMA displayed higher affinity than METH and it was higher for heteromeric than for alpha7 subtype. Preincubation of differentiated PC12 cells with MDMA or METH induces nicotinic acetylcholine receptors (nAChR) up-regulation in a concentration- and time-dependent manner, as many nicotinic ligands do, supporting their functional interaction with nAChRs. Such interaction expands the pharmacological profile of amphetamines and can account for some of their effects.
Note: Podeu consultar el llibre complet a: http://hdl.handle.net/2445/32392
Note: Reproducció del capítol 7 del llibre publicat a: http://www.trnres.com/ebookcontents.php?id=149
It is part of: Recent Advances in Pharmaceutical Sciences, 2011, Chapter 7, p. 155-174, Editor: Diego Muñoz-Torrero
URI: http://hdl.handle.net/2445/21373
Related resource: http://hdl.handle.net/2445/32392
Appears in Collections:Llibres / Capítols de llibre (Farmacologia, Toxicologia i Química Terapèutica)

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