Comparison of gabapentin with other antiepileptic and GABAergic drugs.
The effect of the experimental antiepileptic drug gabapentin (1-(aminomethyl) cyclohexane acetic acid; GPT) on the feline trigeminal complex was compared with the effect of established antiepileptic drugs and with the effect of GABAA and GABAB agonists and antagonists. Intravenous injection of 10-60 mg/kg GPT depressed the descending periventricular facilitation of trigeminal nucleus neurons, as well as segmental excitatory mechanisms. On the other hand, GPT usually facilitated, but sometimes depressed, both segmental and periventricular inhibitory mechanisms. GPT thus resembled carbamazepine and phenytoin in its action on excitatory mechanisms and on segmental inhibition, but differed in its effect on inhibitory pathways descending from the reticular formation. In agreement with our observations, GPT has been found to be effective against partial and generalized tonic-clonic seizures, similar to the spectrum of activity of carbamazepine and phenytoin. The action of GPT in our model also resembled that of the GABAB agonist baclofen in its facilitation of reticular and segmental inhibitory mechanisms and its depression of segmental excitatory mechanisms, but differed in its effect on excitatory mechanisms descending from the reticular formation. GPT has also been reported to mimic GABAB receptor activation in other experiments but appeared to act by a GABA-receptor independent mechanism.
Kondo
T
T
Department of Neurology, University of Pittsburgh School of Medicine, PA 15261.
Fromm
G H
GH
Schmidt
B
B
D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D002415:Cats; D003509:Cyclohexanecarboxylic Acids; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology*; D000077206:Gabapentin; D007275:Injections, Intravenous; D008442:Maxillary Nerve / Q000502:physiology; D010672:Phenytoin / Q000494:pharmacology; D011930:Reaction Time; D014278:Trigeminal Nuclei / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D000077206:Gabapentin