Analysis of seizures induced by a catechol-derivative

Summary

A drug, H13/04, with the structure of a catechol-amide, was found to evoke sound-induced seizures when injected into mice normally resistant to audiogenic seizures. The seizures produced appear to be age-related with maximal seizures elicited at 21–28 days postnatal age. This age pattern corresponds to the age-response pattern present in genetically seizure-sensitive strains of mice. The H13/04-evoked seizures can be prevented by pretreating the mice with l-dihydroxyphenylalanine or 5-hydroxytryptophan. Also clonidine, considered a noradrenaline receptor-stimulating agent, was protective against the drug-induced seizures. The pharmacological studies suggested the importance of noradrenaline in the protection against sound-induced seizures. Biochemical determinations of noradrenaline, dopamine and 5-hydroxytryptamine in the brain suggest an interaction between noradrenaline and serotonin which may be related to the age-dependent aspects of seizures. H13/04 was not effective in reverting genetically-sensitive strains of mice to a high incidence of sound-induced seizures at an age when they normally develop resistance. This observation indicates that H13/04 is specific for induction of sound-induced seizures and does not act just as a general convulsive agent. In young animals at 21 days of age, H13/04 also elicits spontaneous seizures and this form of seizure can be prevented by pretreating the mice with sodium phenobarbital at a dose of 7 mg/kg. Such pretreatment does not, however, prevent the sound-induced seizure. Hence the drug H13/04 will be extremely useful in delineating mechanisms underlying seizure activity, particularily those related to age-dependent seizure activity.