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Memantine alleviates toxicity induced by dichlorvos in rats. J Occup Health 2005 Mar;47(2):96-101

Date

04/13/2005

Pubmed ID

15824473

DOI

10.1539/joh.47.96

Abstract

The changes of N-methyl-D-aspartate (NMDA) receptor and protective efficacy of memantine (MEM) in rats poisoned with dichlorvos were studied. Dichlorvos evoked down-regulation of the affinity and density of [(3)H]MK-801 binding to NMDA receptor in the brain of rats receiving dichlorvos (15 and 25 mg/kg bw, i.p.). The binding capacity of NMDA receptor and acetylcholinesterase activity were determined at 4 h, 8 h, 16 h, 24 h and 48 h after treatment. When rats were given a different doses of MEM (5, 15 and 45 mg/kg bw) after poisoning (dichlorvos 25 mg/kg bw), the latency of onset of signs was postponed and the magnitude of muscular fasciculation was alleviated as the dose of MEM increased. The lower doses of MEM (5 and 15 mg/kg bw) could antagonize the dichlorvos-evoked down-regulation of NMDA receptor, while the highest dose (45 mg/kg bw) decreased the Bmax and Kd values of NMDA receptors. These results show the dichlorvos-evoked down-regulation of NMDA receptor might be self-regulation by the body to protect the central nervous system. MEM could antagonize the down-regulation of NMDA receptors, and alleviated signs of poisoning, especially reducing the magnitude of muscular fasciculation. We suggest that the role of NMDA receptor in organophosphates (OP) poisoning should receive more attention, and, that MEM treatment in acute OP poisoning, as a supplement to atropine and oxime, should be considered.

Author List

Zhou Z, Dai X, Gu X, Sun Y, Zheng G, Zheng J

Author

Yunguang Sun MD, PhD Assistant Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acetylcholinesterase
Animals
Brain
Dichlorvos
Excitatory Amino Acid Antagonists
Insecticides
Male
Memantine
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a