Psychopharmacology
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Comparative Study Clinical Trial
Thiopental and midazolam do not seem to impede metabolism of glutamate in brain-injured patients.
Increased extracellular glutamate levels are related to glial and neuronal damage. Glutamate-mediated toxicity is limited by glial uptake and metabolic transformation of glutamate to glutamine and the energetic compounds alanine and lactate which are utilized by surrounding neurons. Under in vitro conditions, barbiturates have been shown to reduce glutamate uptake and its further metabolism, possibly impeding metabolic coupling between astrocytes and neurons. ⋯ During long-term administration of thiopental and midazolam, pathologically elevated ventricular CSF glutamate levels were associated with significantly increased glutamine and alanine levels up to 14 days after trauma. CSF lactate, however, remained normal. These data suggest that long-term administration of thiopental and midazolam under clinical conditions does not impede enzymatic activities responsible for detoxification and metabolism of glutamate.