Next Article in Journal
Regeneration of Hair Cells: Making Sense of All the Noise
Next Article in Special Issue
A Role for Sigma Receptors in Stimulant Self Administration and Addiction
Previous Article in Journal / Special Issue
Orexin Receptor Targets for Anti-Relapse Medication Development in Drug Addiction
Article Menu

Export Article

Open AccessReview
Pharmaceuticals 2011, 4(6), 822-847; doi:10.3390/ph4060822

Neuronal Nicotinic Receptors as New Targets for Amphetamine-Induced Oxidative Damage and Neurotoxicity

Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, 08028 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Received: 7 April 2011 / Revised: 3 June 2011 / Accepted: 7 June 2011 / Published: 15 June 2011
(This article belongs to the Special Issue Drug Abuse Targets)
View Full-Text   |   Download PDF [658 KB, uploaded 15 June 2011]   |  

Abstract

Amphetamine derivatives such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) are widely abused drugs 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 a7 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, a7 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 a7 and heteromeric nAChR, with MDMA showing lower Ki values, while fluorescence calcium experiments indicated that MDMA behaves as a partial agonist on a7 and as an antagonist on heteromeric nAChR. Sustained Ca increase led to calpain and caspase-3 activation. In addition, modulatory effects of MDMA on a7 and heteromeric nAChR populations have been found. View Full-Text
Keywords: MDMA; methamphetamine; nicotinic; neuroprotection; calcium influx MDMA; methamphetamine; nicotinic; neuroprotection; calcium influx
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Pubill, D.; Garcia-Ratés, S.; Camarasa, J.; Escubedo, E. Neuronal Nicotinic Receptors as New Targets for Amphetamine-Induced Oxidative Damage and Neurotoxicity. Pharmaceuticals 2011, 4, 822-847.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Pharmaceuticals EISSN 1424-8247 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top