Histamine and Seizures : Implications for the Treatment of Epilepsy

Experimental studies have indicated that the central histaminergic neuron system plays an important role in the inhibition of seizures through stimulation of histamine H1 receptors, especially in the developmental period. This has therapeutic implications for currently available drugs that act at histamine receptors. H1 receptor antagonists, including classical antihistamines and anti-allergy drugs, occasionally induce convulsions in healthy children and patients with epilepsy. In particular, promethazine, carbinoxamine, mepyramine (pyrilamine) and ketotifen should be used with caution in these patients. These drugs are widely used as components of over-the-counter medications. The use of the d-chlorphenamine (d-chlorpheniramine) activation study with EEG monitoring is useful for assessing the seizure susceptibility of patients who have had convulsions secondary to administration of H1 receptor antagonists.H2 receptor antagonists have also occasionally been reported to induce convulsions in critically ill and polymedicated patients, and patients with chronic renal or hepatic failure. However, experimental findings have not been consistent with these clinical reports, such that the role of these receptors and their ligands in inducing seizures cannot be confirmed.Recently, H3 receptor antagonists, which enhance endogenous histamine release in the brain, have been demonstrated to have a potent anticonvulsant action. Therefore, these compounds may represent a new avenue for the development of antiepileptic drugs. Considering that H3 receptor antagonists also induce arousal patterns on the EEG, it is possible that they will not be associated with the sedative effects of many conventional antiepileptic drugs.