Changes in motor cortical excitability in humans following orally administered theophylline.
The effects of theophylline on human corticospinal excitability were studied using transcranial magnetic stimulation (TMS) before and after double-blind oral administration of theophylline or placebo in 20 healthy volunteers. TMS measurements included resting and active motor threshold, silent period, intracortical inhibition (ICI), and intracortical facilitation. F-wave and compound muscle action potential (CMAP) were also measured. Theophylline produces a reduction in ICI, while other parameters of corticospinal excitability remained unaffected. Since ICI is thought to depend on GABAA intracortical inhibitory mechanisms, our data suggest that the increase of human motor cortex excitability is the result of a decrease in GABAergic transmission. Our results further support the hypothesis that theophylline might induce convulsions by inhibiting GABAA receptor binding.
Nardone
R
R
Department of Neurology, F. Tappeiner Hospital, Via Rossini 5, 39012 Merano (BZ), Italy. raffaele.nardone@asbmeran.o-it
Buffone
E
E
Covi
M
M
Lochner
P G
PG
Tezzon
F
F
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D003292:Convulsants / Q000494:pharmacology*; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation / Q000295:instrumentation / Q000379:methods; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006801:Humans; D008280:Magnetics; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D011712:Pyramidal Tracts / Q000187:drug effects* / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects; D011963:Receptors, GABA-A / Q000378:metabolism; D012016:Reference Values; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013806:Theophylline / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D003292:Convulsants; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D013806:Theophylline