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Constipation enhances the propensity to seizure in pentylenetetrazole-induced seizure models of mice.

Abstract
Epilepsy is characterized by spontaneous recurrent seizures and represents one of the most frequent neurological diseases, affecting about 60 million people worldwide. The cellular and neurocircuit bases of epilepsy are poorly understood. Constipation is a common gastrointestinal disorder characterized by symptoms such as straining, hard stool, and infrequent defecation. Population-based studies have shown that the prevalence of constipation is up to 30% of the population in developed countries. The causal link between seizure and constipation is a common belief among patients and physicians, but there are no scientific data to support this association. The current investigation evaluated the effects of constipation induced by loperamide (a peripheral μ-opioid receptor agonist without effect on central nervous system receptors) and clidinium (a quaternary amine antimuscarinic agent with reduced central nervous system effects) on two different seizure models of mice: (1) myoclonic, clonic, and generalized tonic seizures and death induced by intraperitoneal administration of pentylenetetrazole and (2) clonic seizure threshold induced by intravenous infusion of pentylenetetrazole. We demonstrated that the measured intestinal transit (%intestinal transit) decreased after loperamide or clidinium treatment for 3days. Constipation in mice which was induced by loperamide or clonidine caused a decrease in threshold to clonic seizure in the intravenous pentylenetetrazole seizure model. Moreover loperamide- or clidinium-induced constipation decreased latencies to, clonic, and tonic seizures and death in the intraperitoneal pentylenetetrazole model of mice. Serum ammonia levels were slightly elevated in both loperamide- and clidinium-treated mice. In conclusion, loperamide- or clidinium-induced constipated mice are more prone to seizure which might confirm the belief of patients and physicians about constipation as a trigger of seizure.
AuthorsLeila Moezi, Fatema Pirsalami, Soroor Inaloo
JournalEpilepsy & behavior : E&B (Epilepsy Behav) Vol. 44 Pg. 200-6 (Mar 2015) ISSN: 1525-5069 [Electronic] United States
PMID25745976 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Antidiarrheals
  • Convulsants
  • Parasympatholytics
  • Quinuclidinyl Benzilate
  • Loperamide
  • clidinium
  • Pentylenetetrazole
Topics
  • Animals
  • Antidiarrheals (toxicity)
  • Constipation (chemically induced, complications)
  • Convulsants (toxicity)
  • Disease Models, Animal
  • Drug Interactions
  • Gastrointestinal Transit
  • Injections, Intraperitoneal
  • Loperamide (toxicity)
  • Male
  • Mice
  • Parasympatholytics (toxicity)
  • Pentylenetetrazole (toxicity)
  • Quinuclidinyl Benzilate (analogs & derivatives, toxicity)
  • Seizures (chemically induced, complications)

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