Proconvulsive effects of histamine H1-antagonists on electrically-induced seizure in developing mice

The purpose of this study was to investigate the developmental differences in seizure susceptibility in mice and the roles of the histaminergic neuron system in inhibition of convulsions in development. First, we studied developmental differences in electrically-induced seizures. Since the 14-day-old mice showed a different seizure pattern from that of older mice, we evaluated the seizure susceptibility of mice older than 21 days. The durations of all the convulsive phases were significantly increased in 21- and 30-day-old mice, compared with older mice. Second, pyrilamine (or mepyramine), ketotifen, and d-chlorpheniramine, centrally-acting H1-antagonists, increased the durations of all the convulsive phases in the 21- and 30-day-old mice, but did not increase duration in 42-day-old mice. Terfenadine and astemizole, H1-antagonists that hardly enter the brain, did not affect the durations of all the convulsive phases in 21-, 30- and 42-day-old mice. The proconvulsant effect of centrally-acting H1-antagonists in 21- and 30-day-old mice were considered to be mediated via the central H1-receptors. Thus, the histaminergic neuron system may have an important physiological role in inhibition of seizures in 21- and 30-day-old mice which have higher seizure susceptibility. This would compensate for the immaturity of the other protective neuron systems such as NMDA receptor complexes and GABA receptors. In conclusion, the present findings support the view that the central histaminergic system plays a role in inhibition of convulsions.