The mechanism of action appears to be mitochondrial toxicity. Vogels, A. P. M., Maas, M. A. W., Daalhuisen, J., Quack G., and Chamuleau, R. A. F. M. 1997. Memantine, a noncompetitive NMDA receptor antagonist improves hyperammonemia-induced encephalopathy and acute hepatic encephalopathy in rats. Hepatic encephalopathy is a complication of end-stage cirrhosis and fulminant hepatic failure. Its pathogenesis is not completely understood, however, it is associated with high concentrations of circulating ammonia.
NMDA receptors bind to and are activated by the neurotransmitters glutamate and aspartate.
Two rat models of hepatic encephalopathy were used, protacaval-shunted rats and complete liver ischemia. Memantine-treated rats also had less brain swelling which often accompanies severe encephalopathy. These results suggest that NMDA receptor over activity may play a role in hyperammonemia-induced hepatic encephalopathy and lead to the development of drugs to treat the condition. A large body of past work has also shown that benzodiazapine receptor antagonists transiently improve hepatic encephalopathy.