title: Proconvulsant effect of ketotifen, a histamine H1 antagonist, confirmed by the use of d-chlorpheniramine with monitoring electroencephalography.
abstract: Ketotifen produced seizures in a 5-year-old boy with secondary generalized epilepsy (SGE) and allergic rhinitis. To confirm that the seizures were due to histamine H1 receptors blockade, d-chlorpheniramine was administered with monitoring electroencephalography (EEG). Administration of d-chlorpheniramine significantly increased the number of epileptic discharges in the patient, compared with those before administration. Plasma noradrenaline and dopamine levels were not affected by treatment with d-chlorpheniramine. These findings indicate that histamine H1 receptors blockade produced convulsions and increased epileptic discharges on EEG. Recently, several experimental reports have shown that histamine has an inhibitory role on convulsions through histamine H1 receptors. Experimental findings and present results show that histamine H1 antagonists have proconvulsant effects, especially in the developmental period. Thus, it is recommended that centrally-acting histamine H1 antagonists should be avoided in epileptic patients, especially in children of pre-school age.
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yokoyama
authors.forename: K
authors.initials: K
authors.lastname: Iinuma
authors.forename: K
authors.initials: K
authors.lastname: Yanai
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: E
authors.initials: E
authors.lastname: Sakurai
authors.forename: K
authors.initials: K
authors.lastname: Onodera
mesh_terms: D002675:Child, Preschool; D002744:Chlorpheniramine / Q000009:adverse effects* / Q000627:therapeutic use; D004298:Dopamine / Q000097:blood; D004569:Electroencephalography / Q000187:drug effects*; D004828:Epilepsies, Partial / Q000150:complications / Q000188:drug therapy; D004837:Epinephrine / Q000097:blood; D006634:Histamine H1 Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007665:Ketotifen / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D009638:Norepinephrine / Q000097:blood; D006255:Rhinitis, Allergic, Seasonal / Q000150:complications / Q000188:drug therapy; D012640:Seizures / Q000139:chemically induced*
chemical_list: D006634:Histamine H1 Antagonists; D002744:Chlorpheniramine; D004298:Dopamine; D007665:Ketotifen; D009638:Norepinephrine; D004837:Epinephrine