The aim of this study was to evaluate the effects of H(1) (
antazoline and
astemizole) or H(2) (
cimetidine and
famotidine)
histamine receptor antagonists on the clonic phase,
tonic seizures and morality of mice challenged with
aminophylline to induce convulsions in mice. Moreover, the total plasma and brain concentrations of
theophylline were evaluated.
Astemizole (1 mg/kg) did not affect the threshold for
aminophylline-induced
seizures, but when administered at a dose of 2 mg/kg, it significantly reduced the CD(50) value of
aminophylline from 249 mg/kg to 211 mg/kg (p < 0.01). The remaining
histamine receptor antagonists studied i.e.,
antazoline (up to 1 mg/kg),
cimetidine (up to 40 mg/kg) and
famotidine (up to 10 mg/kg) had no impact on seizure susceptibility in
aminophylline-induced convulsions. Furthermore,
astemizole (2 mg/kg) decreased latency to the clonic phase of
aminophylline-induced convulsions from 51.1 +/- 4.5 to 32.1 +/- 4.3 min (p < 0.01). It is noteworthy that
astemizole, a novel H(1) receptor antagonist, did not alter the brain and plasma levels of
theophylline, so the existence of pharmacokinetic interactions was excluded. Our results indicate that some interactions between methylxanthines and
histamine receptor antagonists may be clinically important since these drugs are usually combined during the treatment of
status asthmaticus.