The neuroprotective properties of gabapentin-lactam.
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.


CONCLUSIONS
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.
Lagrèze
W A
WA
Department of Ophthalmology, Albert-Ludwigs University of Freiburg, Germany. lagreze@ukl.uni-freiburg.de
Müller-Velten
R
R
Feuerstein
T J
TJ
D000818:Animals; D001372:Aza Compounds / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007511:Ischemia / Q000150:complications; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000209:etiology / Q000517:prevention & control; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D012171:Retinal Vessels; D013141:Spiro Compounds / Q000494:pharmacology*; D013997:Time Factors
D001372:Aza Compounds; D018696:Neuroprotective Agents; D013141:Spiro Compounds; C404763:gabapentin-lactam