Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury?

By C. Ikonomidou, L. Turski. Lancet Neurology, 2002

734 citations recorded by the source corpus.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/5bba8bace03ade19b14e7e73591ed7895367335d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. Eng H. Lo
2. A. Sheldon
3. M. Robinson
4. Y. Wang
5. Ann Marie Craig
6. T. Lai

In Developmental Neuroscience

1. Eng H. Lo
2. Ann Marie Craig

In Neurology

1. Eng H. Lo

Citations in the corpus

• Blood-brain barrier pathophysiology in traumatic brain injury (2011, background): “It has also been proposed that in the later stage post-injury, glutamate may actually promote neuronal survival [73].”
• Glutamate Receptor Ion Channels: Structure, Regulation, and Function (2010, background): “There is also strong evidence indicating that NMDA receptor inhibition can impede recovery of function of neurons damaged but not killed during ischemia (Yu et al., 2001; Ikonomidou and Turski, 2002).”
• A new penumbra: transitioning from injury into repair after stroke (2008, background): “Taken together, in retrospect, these analyses suggest that an untitrated and wholesale blockade of NMDA receptors might not have been an optimal strategy for stroke treatmen”
• Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders (2010, neutral): “The destructive effects of NMDAR activity are in striking contrast to the observation that the survival of several types of neuron is dependent on synaptic NMDAR activity and functio”
• The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention. (2007, background): “It is not completely clear why these efforts were not successful, although some of these agents have neurotoxic effects (for review, see Ikonomidou and Turski, 2002).”
• A key role for TRPM7 channels in anoxic neuronal death. (2003, background): “The paradoxical failure1Toronto Western Hospital Research Institute 11-416 MC-PAV of AET in the face of a clear role for excitotoxicity in acute neurological disorders is unexplained (Birmingham,399 Bathurst Street Toronto, Ontario 2002; Ikonomidou and Turski, 2002).”
• NMDA Receptor Subunits Have Differential Roles in Mediating Excitotoxic Neuronal Death Both In Vitro and In Vivo (2007, background): “…also provide a molecular basis to explain the paradoxical roles of NMDA receptor antagonism in producing extensive neuronal apoptosis in developing animals (Ikonomidou et al., 1999) and neuroprotection against ischemic brain damage in animal studies (Lee et al., 1999; Arundine and Tymianski, 2004).”