advertisement
Abstract #18339 Published in IGR 3-3
The neuroprotective properties of gabapentin-lactam
Lagrèze WA; Müller-Velten R; Feuerstein TJGraefe's Archive for Clinical and Experimental Ophthalmology 2001; 239: 845-849
BACKGROUND: Gabapentin-lactam (GBP-L) is a derivative of the anti-convulsant 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, the authors 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 one hour. Two weeks later, neuronal damage in the ganglion cell layer was quantified histologically. 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 one, two, three, four, and five hours after onset of reperfusion. Subgroups 5b and 5c received 50 and 25 mg/kg, respectively, three hours after reperfusion. Each injection was repeated once after six hours. RESULTS: The proportions of neurons that survived in groups 1-7 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. CONCLUSIONS: GBP-L was neuroprotective in an animal model of acute retinal ischema, even when given up to four hours after reperfusion. GBP-L may prove useful in optic neuropathies such as glaucoma.
Dr W.A. Lagrèze, Department of Ophthalmology, Albert-Ludwigs University of Freiburg, Killianstrasse 5, 79102 Freiburg, Germany. lagreze@ulk.uni-freiburg.de
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)