Glutamate, GABA and excitotoxicity
Glutamate and GABA receptors, the glutamate-glutamine cycle, how ischaemia and prolonged seizures turn glutamate into a toxin, and how receptor changes explain benzodiazepine-resistant status epilepticus, alcohol withdrawal and the actions of ketamine, memantine, baclofen and vigabatrin.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Glutamate is the main excitatory transmitter in the CNS; GABA is the main inhibitory one in the brain, and glycine in the spinal cord and brainstem.
- Glutamate is cleared by astrocyte transporters (EAAT1 and EAAT2), not by an enzyme in the cleft. Astrocytes turn it into glutamine with glutamine synthetase, which also fixes ammonia.
- Excitotoxicity is neuronal death from excessive glutamate receptor activation, driven by calcium entry through NMDA receptors. It is a shared final pathway in stroke, prolonged seizures, trauma and hypoglycaemia.
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Sources
- Principles of Neural Science (6th ed.)McGraw Hill (Kandel, Koester, Mack and Siegelbaum, 2021), 2021
- Australian Medicines HandbookAU/NZAustralian Medicines Handbook Pty Ltd, 2026
- Hill MD et al. Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1). Lancet 2020;395:878-87The Lancet, 2020
- Naylor DE, Liu H, Wasterlain CG. Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus. J Neurosci 2005;25:7724-33Journal of Neuroscience, 2005
- Maguire MJ et al. Prevalence of visual field loss following exposure to vigabatrin therapy: a systematic review. Epilepsia 2010;51:2423-31Epilepsia, 2010
- Miller RG et al. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev 2012;(3):CD001447Cochrane, 2012
- Last updated
- 14 November 2026
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