GABA potentiation: a logical pharmacological approach for the treatment of acute ischaemic stroke

Neuropharmacology. 2000 Jul 10;39(9):1483-94. doi: 10.1016/s0028-3908(99)00233-6.


It has been shown that enhancing the function of the major inhibitory neurotransmitter GABA decreases glutamatergic activity in the brain. Since increased glutamatergic activity is the major primary event that results in cell death following an acute hypoxic-ischaemic stroke, GABAmimetic drugs might therefore be expected to be neuroprotective. This review examines the evidence that GABAergic function is acutely depressed following an ischaemic insult, and also reviews the data that suggest that increasing cerebral GABA concentration has a neuroprotective effect, as does the administration of some (but not all) GABAmimetic agents. The GABA uptake inhibitor CI-966, the GABA(A) agonist muscimol and the GABA(A)mimetic clomethiazole have all been shown to be neuroprotective in animal models of stroke when given after the ischaemic insult. In contrast, benzodiazepines and particularly barbiturates, although potent GABA(A) potentiators, have shown little promise as neuroprotectants. The diversity of GABA(A) receptor subtypes and the in vivo efficacy of certain GABA(A) receptor ligands in animal models of stroke suggests that GABAmimetic drugs are an undervalued approach to stroke therapy.

Publication types

  • Review

MeSH terms

  • Acute Disease
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Brain Ischemia / prevention & control*
  • Chlormethiazole / pharmacology
  • GABA Agonists / pharmacology*
  • Humans
  • Muscimol / pharmacology
  • Neuroprotective Agents / pharmacology*
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism
  • gamma-Aminobutyric Acid / metabolism


  • GABA Agonists
  • Neuroprotective Agents
  • Receptors, GABA-A
  • Chlormethiazole
  • Muscimol
  • gamma-Aminobutyric Acid