BACKGROUND: Gabapentin-lactam (GBP-L) is a derivative of the anti-convulsivant drug gabapentin. In vitro, GBP-L diminished the hypoxia-induced release of the neurotransmitter and excitotoxin glutamate. This effect could be reversed with glibenclamide, indicating that GBP-L acts as an opener of ATP-sensitive potassium channels. In vivo, GBP-L was neuroprotective in a rat model of acute retinal ischemia. In this study we investigated the time- and dose-effect relationship of this neuroprotection. METHODS: In each treatment group (n=9), retinal ischemia was induced in the left eye by pumping air into the anterior chamber to an intraocular pressure of 120 mmHg for 1 h. Two weeks later, neuronal damage in the ganglion cell layer was histologically quantified. Group 1 received vehicle only; group 2 received 75 mg/kg GBP-L i.p. at the beginning of ischemia; groups 3, 4, 5, 6, and 7 received the same dose at 1, 2, 3, 4, and 5 h after onset of reperfusion. Subgroups 5b and 5c received 50 and 25 mg/kg, respectively, 3 h after reperfusion. Each injection was repeated once after 6 h. RESULTS: The proportions of neurons that survived in groups 1 to 7 were 28%, 70%, 59%, 55%, 58%, 45%, and 37%, respectively. The proportions of neurons surviving in groups 5b and 5c were 49% and 39%, respectively. The difference in neuronal survival between group 1 and groups 2, 3, 4, 5, 5b, and 6 was statistically significant. CONCLUSION: GBP-L was neuroprotective in an animal model of acute retinal ischemia, even when given up to 4 h after reperfusion. GBP-L may prove useful in optic neuropathies such as glaucoma.
BACKGROUND:Gabapentin-lactam (GBP-L) is a derivative of the anti-convulsivant drug gabapentin. In vitro, GBP-L diminished the hypoxia-induced release of the neurotransmitter and excitotoxin glutamate. This effect could be reversed with glibenclamide, indicating that GBP-L acts as an opener of ATP-sensitive potassium channels. In vivo, GBP-L was neuroprotective in a rat model of acute retinal ischemia. In this study we investigated the time- and dose-effect relationship of this neuroprotection. METHODS: In each treatment group (n=9), retinal ischemia was induced in the left eye by pumping air into the anterior chamber to an intraocular pressure of 120 mmHg for 1 h. Two weeks later, neuronal damage in the ganglion cell layer was histologically quantified. Group 1 received vehicle only; group 2 received 75 mg/kg GBP-L i.p. at the beginning of ischemia; groups 3, 4, 5, 6, and 7 received the same dose at 1, 2, 3, 4, and 5 h after onset of reperfusion. Subgroups 5b and 5c received 50 and 25 mg/kg, respectively, 3 h after reperfusion. Each injection was repeated once after 6 h. RESULTS: The proportions of neurons that survived in groups 1 to 7 were 28%, 70%, 59%, 55%, 58%, 45%, and 37%, respectively. The proportions of neurons surviving in groups 5b and 5c were 49% and 39%, respectively. The difference in neuronal survival between group 1 and groups 2, 3, 4, 5, 5b, and 6 was statistically significant. CONCLUSION:GBP-L was neuroprotective in an animal model of acute retinal ischemia, even when given up to 4 h after reperfusion. GBP-L may prove useful in optic neuropathies such as glaucoma.
Authors: Huifang Li; Kevin D Graber; Sha Jin; Whitney McDonald; Ben A Barres; David A Prince Journal: Neurobiol Dis Date: 2012-07-02 Impact factor: 5.996
Authors: Birgit Zucker; Dagmar E Ludin; Thomas A Gerds; Carl H Lücking; G Bernhard Landwehrmeyer; Thomas J Feuerstein Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2004-07-30 Impact factor: 3.000
Authors: Jerry P Jasinski; Ray J Butcher; Q N M Hakim Al-Arique; H S Yathirajan; B Narayana Journal: Acta Crystallogr Sect E Struct Rep Online Date: 2009-12-16