PMID- 18455739
OWN - NLM
STAT- MEDLINE
DCOM- 20080825
LR  - 20161124
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 54
IP  - 8
DP  - 2008 Jun
TI  - Memantine protects against amphetamine derivatives-induced neurotoxic damage in 
      rodents.
PG  - 1254-63
LID - 10.1016/j.neuropharm.2008.04.003 [doi]
AB  - We hypothesize that 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine 
      (METH) interact with alpha-7 nicotinic receptors (nAChR). Here we examine whether 
      memantine (MEM), an antagonist of NMDAR and alpha-7 nAChR, prevents MDMA and METH 
      neurotoxicity. MEM prevented both serotonergic injury induced by MDMA in rat and 
      dopaminergic lesion by METH in mice. MEM has a better protective effect in front 
      of MDMA- and METH-induced neurotoxicity than methyllycaconitine (MLA), a specific 
      alpha-7 nAChR antagonist. The double antagonism that MEM exerts on NMDA receptor 
      and on alpha-7 nAChR, probably contributes to its effectiveness. MEM inhibited 
      reactive oxygen species production induced by MDMA or METH in synaptosomes. This 
      effect was not modified by NMDA receptor antagonists, but reversed by alpha-7 
      nAChR agonist (PNU 282987), demonstrating a preventive effect of MEM as a result 
      of it blocking alpha-7 nAChR. In synaptosomes, MDMA decreased 5-HT uptake by 
      about 40%. This decrease was prevented by MEM and by MLA but enhanced by PNU 
      282987. A similar pattern was observed when we measured the dopamine transport 
      inhibited by METH. The inhibition of both transporters by amphetamine derivatives 
      seems to be regulated by the calcium incorporation after activation of alpha-7 
      nAChR. MDMA competitively displaces [(3)H]MLA from rat brain membranes. MEM and 
      METH also displace [(3)H]MLA with non-competitive displacement profiles that fit 
      a two-site model. We conclude that MEM prevents MDMA and METH effects in rodents. 
      MEM may offer neuroprotection against neurotoxicity induced by MDMA and METH by 
      preventing the deleterious effects of these amphetamine derivatives on their 
      respective transporters.
FAU - Chipana, C
AU  - Chipana C
AD  - Unitat de Farmacologia i Farmacognosia, Facultat de Farmacia, Universitat de 
      Barcelona, Avda Joan XXIII s/n, Zona Universitaria Pedralbes, 08028 Barcelona, 
      Spain.
FAU - Torres, I
AU  - Torres I
FAU - Camarasa, J
AU  - Camarasa J
FAU - Pubill, D
AU  - Pubill D
FAU - Escubedo, E
AU  - Escubedo E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080409
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Benzamides)
RN  - 0 (Bridged Bicyclo Compounds)
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Hallucinogens)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (PNU-282987)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 44RAL3456C (Methamphetamine)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - W8O17SJF3T (Memantine)
SB  - IM
MH  - Animals
MH  - Benzamides/pharmacology
MH  - Body Temperature/drug effects
MH  - Bridged Bicyclo Compounds/pharmacology
MH  - Dizocilpine Maleate/pharmacology
MH  - Dopamine Antagonists/*therapeutic use
MH  - Dopamine Plasma Membrane Transport Proteins/genetics/metabolism
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - *Hallucinogens
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - Memantine/*therapeutic use
MH  - *Methamphetamine
MH  - Mice
MH  - *N-Methyl-3,4-methylenedioxyamphetamine
MH  - Neuroglia/drug effects
MH  - *Neuroprotective Agents
MH  - Neurotoxicity Syndromes/*prevention & control
MH  - Prefrontal Cortex/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Nicotinic/drug effects
MH  - Serotonin Plasma Membrane Transport Proteins/genetics/metabolism
EDAT- 2008/05/06 09:00
MHDA- 2008/08/30 09:00
CRDT- 2008/05/06 09:00
PHST- 2007/11/18 00:00 [received]
PHST- 2008/03/13 00:00 [revised]
PHST- 2008/04/02 00:00 [accepted]
PHST- 2008/05/06 09:00 [pubmed]
PHST- 2008/08/30 09:00 [medline]
PHST- 2008/05/06 09:00 [entrez]
AID - S0028-3908(08)00097-X [pii]
AID - 10.1016/j.neuropharm.2008.04.003 [doi]
PST - ppublish
SO  - Neuropharmacology. 2008 Jun;54(8):1254-63. doi: 10.1016/j.neuropharm.2008.04.003. 
      Epub 2008 Apr 9.