title: Gabapentin-lactam, a close analogue of the anticonvulsant gabapentin, exerts convulsant activity in amygdala kindled rats.
abstract: The cyclic GABA analogue gabapentin (GBP), which recently has been marketed for treatment of epilepsy, is particularly effective against complex-partial seizures as occurring in temporal lobe epilepsy. In the present study, we compared the effects of GBP and its lactam analogue (GBP-L) in the amygdala kindling model of temporal lobe epilepsy. In fully kindled rats, GBP (50 mg/kg and 100 mg/kg i.p.) dose-dependently increased the threshold for focal seizures and inhibited the progression from focal to generalized seizures. This effect was not associated with any marked adverse effects. In contrast, GBP-L (10-50 mg/kg) induced myoclonic activity and generalized clonic seizures in kindled rats, demonstrating a striking qualitative difference between the two compounds. By comparison with non-kindled rats it was shown that kindling markedly enhanced the sensitivity of rats to the convulsant activity of GBP-L. The finding that the anticonvulsant efficacy of GBP is lost by lactam formation indicates that GBP and GBP-L differ in their mechanism(s) of action.
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Potschka
authors.forename: T J
authors.initials: TJ
authors.lastname: Feuerstein
authors.forename: W
authors.initials: W
authors.lastname: Löscher
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids; D004305:Dose-Response Relationship, Drug; D005260:Female; D000077206:Gabapentin; D007696:Kindling, Neurologic / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013141:Spiro Compounds / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid
chemical_list: D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D001372:Aza Compounds; D003292:Convulsants; D003509:Cyclohexanecarboxylic Acids; D013141:Spiro Compounds; C404763:gabapentin-lactam; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin