Midazolam and ketamine inhibit glutamate release via a cloned human brain glutamate transporter.

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Sakai F, Amaha K

Midazolam and ketamine inhibit glutamate release via a cloned human brain glutamate transporter.

Can J Anaesth. 2000 Aug;47(8):800-6. doi: 10.1007/BF03019485.

PubMed ID

10958099 [ View in PubMed

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Abstract

PURPOSE: In cerebral ischemia/anoxia, the glutamate transporter runs in reverse and releases glutamate into the extracellular space, causing irreversible neuronal damage. Intravenous anesthetics attenuate overall glutamate release and prevent neuronal injury during anoxia/ischemia, but their effect on the glutamate transporter is variable. METHODS: A human glial glutamate transporter (hGLT-I) cDNA was isolated by screening a human cerebral cortical library. Cloned cDNA was transfected in Chinese hamster ovary cells. The effect of the intravenous anesthetics midazolam (0.3 to 30 microM), ketamine (10 to 100 microM), thiopental (30 to 300 microM), and propofol (3 to 30 microM) on reversed uptake of L-glutamate via hGLT-I was examined by whole-cell patch-clamp. RESULTS: Midazolam at a concentration 3 microM reduced outward currents arising from reversed L-glutamate uptake via hGLT-I in a concentration-dependent manner. While, ketamine at 100 microM attenuated the same outward currents, to 53.3+/-11.4% of those seen in controls without anesthetics (P<0.05, n=5). In contrast, neither thiopental nor propofol showed effects on outward currents mediated by reversed operation of hGLT-I. CONCLUSIONS: These results suggest that midazolam and ketamine, but not thiopental and propofol, have a capacity to inhibit glutamate release via GLT- I directly.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Midazolam	Excitatory amino acid transporter 2	Protein	Humans	No	Inhibitor	Details