The role of central histaminergic neuron system as an anticonvulsive mechanism in developing brain

Experimental and epidemiological studies have indicated that central histaminergic neuron system plays an important role in inhibition of convulsive disorders through histamine H1-receptors, especially in developing period. Histamine H1 antagonists increase the duration of electrically induced convulsions in 21-day-old mice, but not in 42-day-old mice. Epidemiological studies suggested that histamine H1 antagonist may be one of the risk factors in febrile convulsions. In histidinemic patients who were considered to have high brain histamine content, the incidence of convulsions was lower than that of ordinary population. The centrally acting histamine H1 antagonists including pyrilamine and ketotifen facilitate the development of amygdaloid kindling in rats, an experimental model of epileptogenic process. On the contrary, epinastine, a histamine H1 antagonist which scarcely enters the brain, shows no facilitation. These findings suggest that the central histaminergic neuron system plays an inhibitory role on the seizure development through central histamine H1-receptors. Recently, three cases has been reported in which West syndrome developed 8–10 days after ketotifen or oxatomide administration. Considering experimental and clinical studies, histamine H1 antagonists may be associated with West syndrome and may be hazardous to infants. Further careful experimental and clinical studies will be required to elucidate the relationships between West syndrome and central histaminergic neuron system.