The neuroprotective properties of gabapentin-lactam.

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.

• Authors: W A Lagrèze, R Müller-Velten, T J Feuerstein
• Journal: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie (Graefes Arch Clin Exp Ophthalmol) Vol. 239 Issue 11 Pg. 845-9 (Nov 2001) ISSN: 0721-832X [Print] Germany
• PMID: 11789865 (Publication Type: Journal Article)

Chemical References

• Aza Compounds
• Neuroprotective Agents
• Spiro Compounds
• gabapentin-lactam

Topics

• Animals
• Aza Compounds (pharmacology)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Ischemia (complications)
• Male
• Neurons (drug effects, pathology)
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Retinal Diseases (etiology, prevention & control)
• Retinal Ganglion Cells (drug effects, pathology)
• Retinal Vessels
• Spiro Compounds (pharmacology)
• Time Factors