Studies on the effects of histaminergic agents on seizure susceptibility in mice

The influence of pharmacological modifications of the functional activity of the central histaminergic system was studied on the susceptibility of mice to pentylenetetrazol-induced minimal (clonic) and maximal (tonic) seizures. Enhancement in the functional activity of the system by central administration of histamine or 4-methylhistamine of peripheral L-histidine loading failed to modify the risk of seizures. By contrast, reduction in histaminergic function was found to alter seizure susceptibility. Brocresine, an inhibitor of histamine synthesis, decreased and increased the risk of pentylenetetrazol-induced minimal and maximal seizures, respectively. Many, but not all, classical anti-histamines (H1 antagonist) and metiamide (H2 antagonist) and metiamide (H2 antagonist) increased minimal seizure susceptibility after periheral and intraventricular administration, respectively.