title: Cytisine inhibits the protective activity of various classical and novel antiepileptic drugs against 6 Hz-induced psychomotor seizures in mice.
abstract: Cytisine (CYT) is a partial agonist of brain α4β2 nicotinic acetylcholine receptors widely used in Central/Eastern Europe for smoking cessation.
  
  
  
  This study evaluated the effect of CYT on the ability of classical and novel antiepileptic drugs to prevent seizures evoked by the 6-Hz test, a model of psychomotor seizures in mice thought as a model of drug-resistant seizures.
  
  
  
  CYT administered intraperitoneally (i.p.) in a dose of 2 mg kg-1significantly inhibited the anticonvulsant activity of lacosamide, levetiracetam, and pregabalin, increasing their median effective doses 50 (ED50) values from 6.88 to 10.52 mg kg-1(P < 0.05) for lacosamide, from 22.08 to 38.26 mg kg-1(P < 0.05) for levetiracetam, and from 40.48 to 64.61 mg kg-1(P < 0.01) for pregabalin, respectively. There were no significant changes in total brain concentrations of lacosamide, levetiracetam, and pregabalin following CYT i.p. administration. CYT administered in a dose of 2 mg kg-1failed to change the protective action of clobazam, clonazepam, phenobarbital, tiagabine, and valproate in the 6-Hz test. Neither CYT (2 mg kg-1) alone nor its combination with the anticonvulsant drugs (at their ED50values from the 6-Hz test) affected motor coordination; skeletal muscular strength and long-term memory, as determined in the chimney; and grip strength and passive avoidance tests, respectively.
  
  
  
  CYT-evoked alterations in the protection provided by some antiepileptic drugs against seizures can be of serious concern for epileptic smokers, who might demonstrate therapeutic failure to lacosamide, levetiracetam, and pregabalin, resulting in possible breakthrough seizure attacks.
authors: Department of Pharmacology, University of Rzeszów, Al. Rejtana 16c, 35-959, Rzeszów, Poland. tutka@umlub.pl.|Centre for Innovative Research in Medical and Natural Sciences, University of Rzeszów, Pigonia 1, 35-959, Rzeszów, Poland. tutka@umlub.pl.
authors: Piotr
authors: P
authors: Tutka
authors: Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, 20-090, Lublin, Poland.
authors: Maria W
authors: MW
authors: Kondrat-Wróbel
authors: Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, 20-090, Lublin, Poland.
authors: Katarzyna
authors: K
authors: Zaluska
authors: Department of Neurology, School of Medicine, University of California-Davis, Sacramento, CA, USA.
authors: Dorota
authors: D
authors: Żółkowska
authors: Centre of Public Health and Health Promotion, Institute of Rural Health, Jaczewskiego 2, 20-950, Lublin, Poland.
authors: Magdalena
authors: M
authors: Florek-Łuszczki
authors: Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, 20-090, Lublin, Poland.|Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-950, Lublin, Poland.
authors: Jarogniew J
authors: JJ
authors: Łuszczki
mesh_terms: D000470:Alkaloids / Q000633:toxicity*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001392:Azocines / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects*; D000077287:Levetiracetam; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018722:Nicotinic Agonists / Q000633:toxicity*; D010634:Phenobarbital / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D010889:Piracetam / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011807:Quinolizines / Q000633:toxicity; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D014635:Valproic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D000927:Anticonvulsants; D001392:Azocines; D000077287:Levetiracetam; D018722:Nicotinic Agonists; D010634:Phenobarbital; D010889:Piracetam; D011807:Quinolizines; D014635:Valproic Acid; C004712:cytisine; D000093843:Quinolizidine Alkaloids
keywords: Cytisine; Epilepsy; Psychomotor seizures; Smoking cessation