Effects of felbamate, gabapentin and lamotrigine on seizure parameters and excitability in the rat hippocampus.
The effects of three new antiepileptic drugs (felbamate, lamotrigine and gabapentin) on the parameters of seizure initiation and termination in one model of reverberatory seizures in the hippocampal-parahippocampal loop in urethane-anesthetized rats were determined. All three of the drugs caused a dose-dependent decrease in the duration of the seizure discharge. Only very high doses of felbamate had a significant effect on seizure initiation. In addition to the seizure model, we tested the three new anti-epileptic drugs for an effect on excitability, on paired-pulse inhibition and on long-term potentiation (LTP) in the dentate gyrus of the urethane-anesthetized rat. None of the drugs altered LTP or excitability. However, gabapentin altered paired-pulse inhibition, causing a loss of inhibition. For felbamate and lamotrigine, the effects of seizure duration are consistent with their clinical effects as antiepileptic drugs. However, the effect of gabapentin on paired-pulse inhibition suggests a proconvulsant effect and the effect on seizure duration suggests an antiepileptic effect.
Xiong
Z Q
ZQ
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA.
Stringer
J L
JL
D000085:Acetates / Q000494:pharmacology; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects*; D000078328:Felbamate; D000077206:Gabapentin; D006624:Hippocampus / Q000187:drug effects*; D000077213:Lamotrigine; D008297:Male; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy; D014227:Triazines / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D048448:Phenylcarbamates; D011409:Propylene Glycols; D014227:Triazines; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000077213:Lamotrigine; D000078328:Felbamate