The effects of gabapentin in the rat hippocampus are mimicked by two structural analogs, but not by nimodipine.
Gabapentin has been shown to reduce paired-pulse inhibition in the dentate gyrus of the urethane-anesthetized rat and has been shown to block calcium channels, but its not known how these possible mechanisms relate to its antiepileptic effect. Here, we tested two structural analogs of gabapentin for the ability to reduce seizure duration and to alter paired-pulse inhibition in the dentate gyrus in urethane anesthetized adult Sprague-Dawley rats. We compared with our results to those with diazepam, an anxiolytic and GABA(A) positive modulator and with nimodipine, a specific blocker of L-type Ca2+ channels. Both structural analogs of gabapentin caused a dose-dependent loss of paired-pulse inhibition and blocked the lengthening of the duration of the seizure discharge. Nimodipine also blocked the increase in duration of the seizure discharge, but increased paired-pulse inhibition. The effects of the GABA derivatives on paired-pulse inhibition and on seizure duration may have a common mechanism. Furthermore, our results indicate that gabapentin's postulated block of L-type calcium channels is not responsible for reducing paired-pulse inhibition. However, calcium channel block could still be the basis for the antiepileptic effect of gabapentin and its analogs.
Stringer
J L
JL
Depurtncnt of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA. janets@bcm.tmc.edu
Taylor
C P
CP
D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids; D003510:Cyclohexanes; D018891:Dentate Gyrus / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D000077206:Gabapentin; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D009553:Nimodipine / Q000494:pharmacology*; D000069583:Pregabalin; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
C112420:(1-(aminomethyl)-3-methylcyclohexyl)acetic acid; D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D003509:Cyclohexanecarboxylic Acids; D003510:Cyclohexanes; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D009553:Nimodipine; D000077206:Gabapentin; D003975:Diazepam