Effect of histamine receptor antagonists on aminophylline-induced seizures and lethality in mice.

Article Details

Citation

Swiader MJ, Luszczki JJ, Wielosz M, Czuczwar SJ

Effect of histamine receptor antagonists on aminophylline-induced seizures and lethality in mice.

Pharmacol Rep. 2005 Jul-Aug;57(4):531-5.

PubMed ID
16129921 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AntazolineHistamine H1 receptorProteinHumans
Yes
Antagonist
Details