Epilepsy is a common neurological disorder characterized by repeated and
spontaneous epileptic seizures, which is not well controlled by current
medication. Traditional theory supports that epilepsy results from the
imbalance of excitatory glutamate neurons and inhibitory GABAergic
neurons. Recently, shreds of evidence from available clinical and
preclinical researches suggest that histamine in the central nervous
system plays an important role in the modulation of neural excitability
and pathogenesis of epilepsy. Many histamine receptor ligands show
positive response in animal epilepsy models, among which the H3R
antagonist pitolisant even has shown a good anti-epileptic effect in
clinical trials. New insights are focusing on the potential action of
histamine receptors to control and treat epilepsy. This review
summarizes the findings from animal and clinical researches on the role
of brain histamine and histamine receptor in epilepsy. Importantly, we
further provide perspectives on some possible research directions for
future studies.