Abstract
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.
Publication types
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Clinical Trial
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Controlled Clinical Trial
MeSH terms
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Action Potentials / drug effects
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Action Potentials / physiology
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Administration, Oral
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Adolescent
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Adult
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Binding, Competitive / drug effects
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Binding, Competitive / physiology
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Convulsants / pharmacology*
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Double-Blind Method
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Down-Regulation / drug effects
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Down-Regulation / physiology
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Electric Stimulation / instrumentation
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Electric Stimulation / methods
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Evoked Potentials, Motor / drug effects
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Evoked Potentials, Motor / physiology
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Female
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GABA Antagonists / pharmacology
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GABA-A Receptor Antagonists
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Humans
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Magnetics
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Male
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Middle Aged
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Motor Cortex / drug effects*
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Motor Cortex / physiology
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Muscle, Skeletal / innervation
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Muscle, Skeletal / physiology
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Neural Inhibition / drug effects*
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Neural Inhibition / physiology
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Pyramidal Tracts / drug effects*
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Pyramidal Tracts / physiology
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Reaction Time / drug effects
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Receptors, GABA-A / metabolism
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Reference Values
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Theophylline / pharmacology*
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gamma-Aminobutyric Acid / metabolism
Substances
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Convulsants
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GABA Antagonists
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GABA-A Receptor Antagonists
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Receptors, GABA-A
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gamma-Aminobutyric Acid
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Theophylline