PMID- 19897077
OWN - NLM
STAT- MEDLINE
DCOM- 20100108
LR  - 20131121
IS  - 2162-5514 (Electronic)
IS  - 0074-7742 (Linking)
VI  - 88
DP  - 2009
TI  - Involvement of nicotinic receptors in methamphetamine- and MDMA-induced 
      neurotoxicity: pharmacological implications.
PG  - 121-66
LID - 10.1016/S0074-7742(09)88006-9 [doi]
AB  - During the last years, we have focused on the study of the neurotoxic effects of 
      3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) on the 
      central nervous system (CNS) and their pharmacological prevention methods. 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) prevents ROS production induced by MDMA and METH. 
      Consequently, in vivo, MLA significantly prevents MDMA- and METH-induced 
      neurotoxicity at dopaminergic level (mouse striatum), without affecting 
      hyperthermia induced by these amphetamines. Additionally, when neuroprotection 
      was assayed with memantine (MEM), a dual antagonist of NMDA and alpha7 receptors, 
      an effective neuroprotection was obtained also ahead of serotonergic injury 
      induced by MDMA in rats. MEM also prevents MDMA effect on serotonin transporter 
      functionality and METH effect on dopamine transporter (DAT), suggesting that 
      behavioral effects of these psychostimulants can also be modulated by MEM. 
      Finally, we have demonstrated that MEM prevents the impaired memory function 
      induced by MDMA, and also, using binding studies with radioligands, we have 
      characterized the interaction of these substances with nicotinic receptors. 
      Studies at molecular level showed that both MDMA and METH displaced competitively 
      the binding of radioligands with homomeric alpha7 and heteromeric nicotinic 
      acetylcholine receptors (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. Pre-incubation of differentiated 
      PC12 cells with MDMA or METH induces nAChR upregulation 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.
FAU - Escubedo, E
AU  - Escubedo E
AD  - Unitat de Farmacologia i Farmacognosia, Facultat de Farmacia, Universitat de 
      Barcelona, Barcelona 08028, Spain.
FAU - Camarasa, J
AU  - Camarasa J
FAU - Chipana, C
AU  - Chipana C
FAU - Garcia-Rates, S
AU  - Garcia-Rates S
FAU - Pubill, D
AU  - Pubill D
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Int Rev Neurobiol
JT  - International review of neurobiology
JID - 0374740
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Nicotinic)
RN  - 44RAL3456C (Methamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/metabolism/pathology
MH  - Central Nervous System Stimulants/*toxicity
MH  - Humans
MH  - Methamphetamine/*toxicity
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Neurotoxicity Syndromes/*metabolism/pathology
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Nicotinic/drug effects/*metabolism
RF  - 178
EDAT- 2009/11/10 06:00
MHDA- 2010/01/09 06:00
CRDT- 2009/11/10 06:00
PHST- 2009/11/10 06:00 [entrez]
PHST- 2009/11/10 06:00 [pubmed]
PHST- 2010/01/09 06:00 [medline]
AID - S0074-7742(09)88006-9 [pii]
AID - 10.1016/S0074-7742(09)88006-9 [doi]
PST - ppublish
SO  - Int Rev Neurobiol. 2009;88:121-66. doi: 10.1016/S0074-7742(09)88006-9.