Different effects of GABAergic anticonvulsants on 4-aminopyridine-induced spontaneous GABAergic hyperpolarizations of hippocampal pyramidal cells--implication for their potency in migraine therapy.
Clinical studies indicate anti-migrane efficacy of the probably GABAergic anticonvulsants valproate and gabapentin. For the GABAergic anticonvulsants vigabatrin and tiagabine, studies about antimigrane efficacy are missing. The aim of this study was to test the GABAergic potency of these drugs in vitro before further clinical studies. Intracellular recordings were obtained from hippocampal pyramidal cells. Spontaneous GABAergic hyperpolarizations (SGH) elicited by 75 microM 4-aminopyridine were used to test the effect of these drugs on GABA-dependent potentials. Tiagabine (0.1 mM) prolonged the duration of SGH. Furthermore, monophasic SGH turned over into triphasic typical GABAergic membrane potential fluctuations within 20 min. In contrast, valproate, gabapentin, and vigabatrin failed to affect SGH up to 60 min of application. The reason for the fast action of tiagabine on SGH may be caused by a faster increase of synaptic GABA levels compared with other drugs. As migraine therapy benefits from an augmentation of GABA activity, we recommend clinical studies of tiagabine as a fast-acting agent in migraine attacks.
Leniger
T
T
Department of Neurology, University of Essen, Germany. tobias.leniger@uni-essen.de
Wiemann
M
M
Bingmann
D
D
Hufnagel
A
A
Bonnet
U
U
D015761:4-Aminopyridine / Q000633:toxicity; D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D003292:Convulsants / Q000633:toxicity; D003509:Cyclohexanecarboxylic Acids; D018755:GABA Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000077206:Gabapentin; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology; D009557:Nipecotic Acids / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D000078308:Tiagabine; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology*; D020888:Vigabatrin / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D000927:Anticonvulsants; D003292:Convulsants; D003509:Cyclohexanecarboxylic Acids; D018755:GABA Agonists; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D000077206:Gabapentin; D015761:4-Aminopyridine; D020888:Vigabatrin; D000078308:Tiagabine