ArticleCNS neuroscience & therapeutics2012
Chronic h1-antihistamine treatment increases seizure susceptibility after withdrawal by impairing glutamine synthetase.
Article in CNS neuroscience & therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Triptolide Inhibits Epileptic Seizures by Rescuing the Neuroinflammation-Related GABAergic Dysfunction in Mice.CNS neuroscience & therapeutics · 2025Article
- First-Generation Antihistamines and Seizures in Young Children.JAMA network open · 2024Article
- Region-independent active CNS net uptake of marketed HFrontiers in cellular neuroscience · 2024Article
- Role of histidine decarboxylase gene in the pathogenesis of Tourette syndrome.Brain and behavior · 2022Review
- The Pro-inflammatory Cytokine Interleukin-1β is a Key Regulatory Factor for the Postictal Suppression in Mice.CNS neuroscience & therapeutics · 2015Article
- Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion.Scientific reports · 2015Article
- Protective effect of carnosine after chronic cerebral hypoperfusion possibly through suppressing astrocyte activation.American journal of translational research · 2015Article
- Gender difference in acquired seizure susceptibility in adult rats after early complex febrile seizures.Neuroscience bulletin · 2014Article
- Aggravation of seizure-like events by hydrogen sulfide: involvement of multiple targets that control neuronal excitability.CNS neuroscience & therapeutics · 2014Article
- Transient lack of glucose but not O2 is involved in ischemic postconditioning-induced neuroprotection.CNS neuroscience & therapeutics · 2013Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the effect of chronic H1-antihistamine treatment on seizure susceptibility after drug withdrawal in nonepileptic rats and to further study its relation to glutamine synthetase (GS), which is the key enzyme for glutamate metabolism and gamma aminobutyric acid (GABA) synthesis.
methodsAfter drug withdrawal from a 2-week treatment with diphenhydramine or pyrilamine, seizure susceptibility was determined by amygdaloid kindling or pentylenetetrazol model; meanwhile, the GS expression or activity was analyzed. The glutamine, glutamate, and GABA contents were measured by high-performance liquid chromatography.
resultsSeizure susceptibility significantly increased in amygdaloid kindling and pentylenetetrazol model 10 days after drug withdrawal from a 2-week treatment with H1-antihistamines. Meanwhile, GS activity and expression in the cortex or hippocampus decreased simultaneously with a marked decline of glutamine and GABA content. Comparable inhibition of GS activity by methionine sulfoximine was also sufficient to increase the susceptibility, while supplementation with glutamine reversed the high susceptibility 10 days after diphenhydramine withdrawal. Moreover, the seizure susceptibility increased 10 days after diphenhydramine withdrawal in wild-type mice but not in histidine decarboxylase knockout mice, which lack histamine.
conclusionsChronic H1-antihistamine treatment produces long-lasting increase in seizure susceptibility in nonepileptic rodents after drug withdrawal and its mechanism involves impairment of GS through blocking the action of histamine.
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