title: [Protective effect of memantine on N-methyl-D-aspartate receptor in dichlorvos-poisoned rat brain].
abstract: OBJECTIVE
  To study the protective effect of memantine on the regulation of N-methyl-D-aspartate (NMDA) receptor in dichlorvos-poisoned rat brain, and to understand the mechanism of its role in organophosphate poisoning.
  
  
  METHODS
  SD rats were administrated dichlorvos (25 mg/kg, ip) then three groups were treated with memantine at doses of 5, 15 and 45 mg/kg respectively. The activity of acetylcholinesterase (AChE) and binding capacity of NMDA receptor with [(3)H]MK-801 were determined 16 h after dichlorvos injection.
  
  
  RESULTS
  The time of onset of toxic symptoms in 15, 45 mg memantine treated groups [(18.40 +/- 1.14) and (21.40 +/- 1.52) min respectively] was higher than that in dichlorvos alone group [(16.75 +/- 1.62) min]; the intensity of muscle fasciculation (1.60 +/- 1.14 and 0.80 +/- 0.84, respectively) was less than that in control group (2.85 +/- 0.37); the total score of poisoning symptoms (8.80 +/- 1.79 and 9.00 +/- 2.24 respectively) was also less than that in dichlorvos group (14.60 +/- 1.70). The AChE activities both in blood and brain of memantine treated groups were not significantly different from those in dichlorvos alone group. The affinity (Kd value) and density (Bmax value) of brain NMDA receptor in dichlorvos exposed rats [(75.55 +/- 7.87) nmol/L, (0.46 +/- 0.06) pmol/mg pro respectively] were higher and lower respectively than those in control group [(37.37 +/- 4.17) nmol/L, (0.62 +/- 0.04) pmol/mg pro respectively]. Lower level of memantine (5 and 25 mg/kg) could antagonize the dichlorvos-evoked down-regulation of [(3)H]MK-801 binding to NMDA receptor in rat brain [Bmax value: (0.55 +/- 0.07) and (0.64 +/- 0.07) pmol/mg pro; Kd value: (38.68 +/- 4.54) and (32.58 +/- 3.90) nmol/L respectively] while higher dose of memantine (45 mg/kg), the Bmax (0.45 +/- 0.06) pmol/mg pro and Kd (22.88 +/- 4.42) nmol/L of NMDA receptor were significantly decreased (P < 0.01).
  
  
  CONCLUSIONS
  Memantine in certain dose range could protect against the down-regulation of NMDA receptor in rat brain, and alleviate organophosphorus poisoning symptoms to some extent. The recovery of AChE activity inhibition wasn't involved in the treatment with memantine on dichlorvos poisoning, therefore, atropine and a proper AChE reactivator (an oxime) should be used clinically.
authors.affiliation: School of Public Health, Fudan University, Shanghai 200032, China.
authors.forename: Xu-feng
authors.initials: XF
authors.lastname: Dai
authors.forename: Zhi-jun
authors.initials: ZJ
authors.lastname: Zhou
authors.forename: Xi-an
authors.initials: XA
authors.lastname: Gu
authors.forename: Yun-guang
authors.initials: YG
authors.lastname: Sun
authors.forename: Guang
authors.initials: G
authors.lastname: Zheng
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004006:Dichlorvos / Q000633:toxicity*; D015259:Dopamine Agents / Q000494:pharmacology; D007306:Insecticides / Q000633:toxicity; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D015259:Dopamine Agents; D007306:Insecticides; D016194:Receptors, N-Methyl-D-Aspartate; D004006:Dichlorvos; D000110:Acetylcholinesterase; D008559:Memantine