Inhibitory effect of theophylline on recombinant GABA(A) receptor

Convulsions due to systemic toxicity are a major and frequently fatal side effect of theophylline. The cause of theophylline-induced convulsions is no t clear, but antagonism of the inhibitory nervous system may be implicated. so we examined the effects of theophylline on GABA-induced currents using recombinant GABA(A) receptor (GABA(A)-R). Theophylline dose-dependently inh ibited GABA-induced currents: the IC50 value was 1841 +/- 63 muM and Hill c oefficient 1.09 +/- 0.03. The inhibitory action of theophylline on GABA-ind uced currents was competitive and voltage dependent. The inhibition of GABA -induced currents by theophylline may be a primary mechanism underlying the ophylline-induced convulsions. NeuroReport 12:489-493 (C) 2001 Lippincott W illiams & Wilkins.