Pregabalin suppresses calcium-mediated proteolysis and improves stroke outcome.
Pregabalin, a Ca(2+) channel α(2)δ-subunit antagonist with analgesic and antiepileptic activity, reduced neuronal loss and improved functional outcome in a mouse model of focal ischemic stroke. Pregabalin administration (5-10mg/kg, i.p.) 30-90 min after transient middle cerebral artery occlusion/reperfusion reduced infarct volume, neuronal death in the ischemic penumbra and neurological deficits at 24h post-stroke. Pregabalin significantly decreased the amount of Ca(2+)/calpain-mediated α-spectrin proteolysis in the cerebral cortex measured at 6h post-stroke. Together with the extensive clinical experience with pregabalin for other neurological indications, our findings suggest the potential for a therapeutic benefit of pregabalin in stroke patients.
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USA.
Jeong Seon
JS
Yoon
Jong-Hwan
JH
Lee
Tae Gen
TG
Son
Mohamed R
MR
Mughal
Nigel H
NH
Greig
Mark P
MP
Mattson
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000069583:Pregabalin; D059748:Proteolysis / Q000187:drug effects*; D020521:Stroke / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D002118:Calcium