title: Nicotine reversal of anticonvulsant action of topiramate in kainic acid-induced seizure model in mice.
abstract: BACKGROUND
  Tobacco smoking is a widespread phenomenon, and nicotine is the addictive component of tobacco. Nicotine acts through nicotinic cholinergic receptors and has been associated with different types of psychophysical disorders in human beings. The present study had explored the proconvulsive action of nicotine and its effect on the antiseizure efficacy of topiramate against kainic acid (KA)-induced seizures in mice.
  
  
  METHODS
  The study had evaluated the dose-response curves for nicotine and KA and for KA in nicotine-pretreated mice and for topiramate against KA-induced seizures. Mecamylamine was used to antagonize the nicotinic receptor-mediated actions of nicotine. CD50 (convulsive dose in 50% of animals) for KA and nicotine and ED50 (effective dose in 50% of animals as anticonvulsant) for topiramate were determined. Brain lipid peroxidation studies were also undertaken in the treated mice.
  
  
  RESULTS
  Nicotine significantly potentiated the convulsive action of KA acid and reduced the CD50 (95% confidence limits [CL]) value for KA from 2.6 mg/kg (2.3-3.1) to 1.4 mg/kg (0.9-2.1), intraperitoneally (i.p.). Topiramate pretreatment significantly inhibited KA-induced seizures and brain lipid peroxidation with ED50 (95% CL) value of 21.90 mg/kg (17.3-28.2), i.p. Nicotine pretreatment caused dose-dependent antagonism to the antiseizure and antilipid peroxidative actions of topiramate. Mecamylamine had antagonized the proconvulsant action of nicotine.
  
  
  CONCLUSIONS
  The study highlights the fact that intake of nicotine, through agonism to nAChR, might predispose epileptic patients to lower seizure threshold and induce a state of refractoriness to the protective effects of the antiepileptic drugs, resulting in possible breakthrough seizure attacks.
authors.affiliation: Department of Pharmacology, Indira Gandhi Medical College, Shimla, India.
authors.forename: Nimisha
authors.initials: N
authors.lastname: Sood
authors.forename: Debasish
authors.initials: D
authors.lastname: Hota
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Sahai
authors.forename: Amitava
authors.initials: A
authors.lastname: Chakrabarti
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005632:Fructose / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D006801:Humans; D007608:Kainic Acid / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D000077236:Topiramate; D005632:Fructose; D008464:Mecamylamine; D009538:Nicotine; D007608:Kainic Acid