The neuroprotective effects of R-phenibut after focal cerebral ischemia

Pharmacol Res. 2016 Nov;113(Pt B):796-801. doi: 10.1016/j.phrs.2015.11.013. Epub 2015 Nov 24.


R-phenibut is a γ-aminobutyric acid (GABA)-B receptor and α2-δ subunit of the voltage-dependent calcium channel (VDCC) ligand. The aim of the present study was to test the effects of R-phenibut on the motor, sensory and tactile functions and histological outcomes in rats following transient middle cerebral artery occlusion (MCAO). In this study, MCAO was induced by filament insertion (f-MCAO) or endothelin-1 (ET1) microinjection (ET1-MCAO) in male Wistar or CD rats, respectively. R-phenibut was administrated at doses of 10 and 50mg/kg for 14 days in the f-MCAO or 7 days in the ET1-MCAO. The vibrissae-evoked forelimb-placing and limb-placing tests were used to assess sensorimotor, tactile and proprioceptive function. Quantitative reverse transcriptase-PCR was used to detect brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) gene expression in the damaged brain hemisphere. Both f-MCAO and ET1-MCAO resulted in statistically significant impairment of sensorimotor function and brain infarction. R-phenibut at a dose of 10mg/kg significantly improved histological outcome at day 7 in the ET1-MCAO. R-phenibut treatment at a dose of 50mg/kg significantly alleviated reduction of brain volume in damaged hemisphere in both f-MCAO and ET1-MCAO. In R-phenibut treated animals a trend of recovery of tactile and proprioceptive stimulation in the vibrissae-evoked forelimb-placing test was observed. After R-phenibut treatment at a dose of 50mg/kg statistically significant increase of BDNF and VEGF gene expression was found in damaged brain hemisphere. Taken together, obtained results provide evidence for the neuroprotective activity of R-phenibut in experimental models of stroke. These effects might be related to the modulatory effects of the drug on the GABA-B receptor and α2-δ subunit of VDCC.

Keywords: BDNF; GABA-B receptors; R-phenibut; Stroke; VEGF; α(2)-δ subunit of VDCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • Calcium Channels / metabolism
  • Disease Models, Animal
  • Eye Proteins / pharmacology*
  • Forelimb / drug effects
  • Forelimb / metabolism
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / metabolism
  • Male
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, GABA-B / metabolism
  • Sensorimotor Cortex / drug effects*
  • Sensorimotor Cortex / metabolism
  • Stroke / drug therapy
  • Stroke / metabolism
  • Vascular Endothelial Growth Factor A / metabolism


  • Brain-Derived Neurotrophic Factor
  • Calcium Channels
  • Eye Proteins
  • Neuroprotective Agents
  • R-photopsin
  • Receptors, GABA-B
  • Vascular Endothelial Growth Factor A