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The neuroprotective properties of gabapentin-lactam

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Abstract.

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.

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Lagrèze, W.A., Müller-Velten, R. & Feuerstein, T.J. The neuroprotective properties of gabapentin-lactam. Graefe's Arch Clin Exp Ophthalmol 239, 845–849 (2001). https://doi.org/10.1007/s00417-001-0383-5

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  • DOI: https://doi.org/10.1007/s00417-001-0383-5

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