Protective effect of memantine on N-methyl-D-aspartate receptor in dichlorvos-poisoned rat brain.
- Author:
Xu-feng DAI
1
;
Zhi-jun ZHOU
;
Xi-an GU
;
Yun-guang SUN
;
Guang ZHENG
;
Jie ZHENG
Author Information
- Publication Type:Journal Article
- MeSH: Acetylcholinesterase; metabolism; Animals; Brain; drug effects; metabolism; Dichlorvos; toxicity; Dopamine Agents; pharmacology; Insecticides; toxicity; Male; Memantine; pharmacology; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; metabolism
- From: Chinese Journal of Industrial Hygiene and Occupational Diseases 2004;22(1):11-14
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSSD 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.
RESULTSThe 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).
CONCLUSIONMemantine 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.
