Blockade of opioid tolerance and dependence by NMDA receptor antagonist

The present review summarizes the effects of drugs that block N-methyl D-aspartate receptor complex (NMDA-RC) on the development of opiate tolerance and abstinence. Using behavioral pharmacological approaches, pre-clinical studies demonstrate that noncompetitive and competitive NMDA receptor antagonists and glycine binding site antagonists can inhibit opioid tolerance and some symptoms of opioid withdrawal. The biochemical mechanisms underlying the inhibition of NMDA receptor antagonists on opioid tolerance and dependence are discussed. There is some extent of neurotoxicity associated with the therapeutic use of NMDA receptor antagonists.