Potential of memantine, D-tubocurarine, and atropine in preventing acute toxic myopathy induced by organophosphate nerve agents: soman, sarin, tabun and VX.

Article Details

Citation

Gupta RC, Dettbarn WD

Potential of memantine, D-tubocurarine, and atropine in preventing acute toxic myopathy induced by organophosphate nerve agents: soman, sarin, tabun and VX.

Neurotoxicology. 1992 Fall;13(3):649-61.

PubMed ID
1475066 [ View in PubMed
]
Abstract

Male Sprague-Dawley rats when administered sc a sublethal dose of organophosphorus cholinesterase inhibitors such as the nerve agents, soman (100 micrograms/kg, sc), sarin (110 micrograms/kg, sc), tabun (200 micrograms/kg, sc), or VX (12 micrograms/kg, sc), developed seizures and severe muscle fasciculations within 15-20 min, lasting for 4-6 hr. Marked inhibition of acetylcholinesterase (AChE) and necrotic lesions in skeletal muscles such as soleus, extensor digitorum longus, and diaphragm were evident between 1-24 hr following injection. Pretreatment with memantine HCl (MEM, 18 mg/kg, sc) together with atropine sulfate (ATS, 16 mg/kg, sc), 60 min and 15 min, respectively, prior to nerve agents attenuated AChE inhibition, prevented myonecrosis, and muscle fasciculations as well as other signs of cholinergic toxicity. Pretreatment combining d-tubocurarine (d-TC, 0.075 mg/kg, sc) and ATS (16 mg/kg, sc) prevented the myonecrosis and fasciculation without protecting AChE against inhibition by these nerve agents. Neither MEM, d-TC, nor ATS in the concentration given interfered with the normal behavior of the rats. The role of d-TC and ATS interaction with presynaptic receptors regulating ACh release and MEM's role in modulating neural hyperactivity as protective mechanisms are discussed.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
TubocurarineAcetylcholinesteraseProteinHumans
Unknown
Inhibitor
Details