N-methyl-D-aspartate (NMDA) and NMDA receptors (NMDAR)

see also:

• neurology
• ketamine

• NMDA is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor
• unlike glutamate, NMDA only binds to and regulates the NMDA receptor and has no effect on other glutamate receptors (such as those for AMPA and kainate)
• NMDA receptors are thought to mediate alcohol withdrawal symptoms such as agitation and perhaps seizure
• at homeostatic levels NMDA plays an essential role as a neurotransmitter and neuroendocrine regulator

• agonist binding to its NR2 subunits results in a non-specific cation channel opening, which can allow the passage of Ca2+ and Na+ into the cell and K+ out of the cell
• will only open if glutamate is in the synapse and concurrently the postsynaptic membrane is already depolarized - acting as coincidence detectors at the neuronal level
• the excitatory postsynaptic potential (EPSP) produced by activation of an NMDA receptor also increases the concentration of Ca2+ in the cell.

• this receptor is critical for promoting physiological synaptic plasticity and neuronal viability.¹⁾

• ketamine
  • GluN2B-containing NMDARs appear to be the main action of ketamine ²⁾
• amantadine
• dextromethorphan (DXM)

• an autoimmune condition, with the primary target of antibodies being the GluN1 subunit of the N-methyl-D-aspartate receptors (NMDAR) in the brain
• rare: one in 1.5 million people per year but is is relatively common compared to other paraneoplastic disorders.
• 80% are female
• can occur at any age but most commonly under age 45yrs
• 1st described in 2007
• https://en.wikipedia.org/wiki/Anti-NMDA_receptor_encephalitis
• aetiology
  • tumours
    • half of cases are associated with tumors, most commonly teratomas of the ovaries
  • Herpes simplex virus (HSV) encephalitis
    • accounts for ~half the cases in children
  • other causes
• clinical features
  • fever, headache, malaise, flu-like illness initially which may precede onset of encephalitis features by days or weeks
  • often followed by delusions and hallucinations with agitation and confusion
  • may then develop seizures or motor disturbances (“piano playing”, “pedalling”), and some develop catatonia
  • 4% mortality rate
  • 10% recurrence rate
• Dx
  • NMDA receptor antibodies can be detected in serum and/or CSF
• Rx
  • remove cause if possible
  • immunosuppression