The effect of antihistamines on seizures induced by increasing-current electroshocks: ketotifen, but not olopatadine, promotes the seizures in infant rats.
Clinical reports have shown that some antihistamines, such as ketotifen, occasionally produced seizures, especially in pre-school age children or young patients with epilepsy. The purpose of this study was to investigate whether olopatadine, one of the most efficacious antihistamines, promotes seizures induced by electroshocks in young rats. We investigated the seizures induced by electroshock using increasing-current delivery in 3- or 4-week-old rats, and found that the threshold-current of tonic extensor seizures was elevated with age in weeks in the vehicle-treatment groups. While caffeine decreased the threshold-current in every age group of rats, pentylenetetrazole, a γ-aminobutyric acid (GABA)(A) receptor antagonist, significantly decreased them only in 4-week-old rats. On the other hand, ketotifen decreased them only in 3-weeks-old rats. In the 3-week-old rats, neither olopatadine nor fexofenadine had any effect on the threshold-currents of tonic extensor seizures. These results showed that histaminergic neuro-transmission in the brain plays a crucial role in inhibiting seizures in rats soon after weaning, but is no longer effective in rats as they approach sexual maturation. In addition, unlike ketotifen, olopatadine, as well as fexofenadine, do not promote the occurrence of seizures in infant rats.
Pharmacological Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd., Shizuoka, Japan. kohji.yamada@kyowa-kirin.co.jp
Koji
K
Yamada
Fumitake
F
Takizawa
Tadafumi
T
Tamura
Tomoyuki
T
Kanda
D000367:Age Factors; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003990:Dibenzoxepins / Q000494:pharmacology*; D004597:Electroshock; D004827:Epilepsy; D018756:GABA Antagonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007665:Ketotifen / Q000494:pharmacology*; D008297:Male; D000069605:Olopatadine Hydrochloride; D010433:Pentylenetetrazole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000209:etiology; D016593:Terfenadine / Q000031:analogs & derivatives / Q000494:pharmacology
D018926:Anti-Allergic Agents; D000697:Central Nervous System Stimulants; D003990:Dibenzoxepins; D018756:GABA Antagonists; D006634:Histamine H1 Antagonists; D000069605:Olopatadine Hydrochloride; D002110:Caffeine; D016593:Terfenadine; C093230:fexofenadine; D010433:Pentylenetetrazole; D007665:Ketotifen