Piotr Tutka1,2, Maria W Kondrat-Wróbel3, Katarzyna Zaluska3, Dorota Żółkowska4, Magdalena Florek-Łuszczki5, Jarogniew J Łuszczki3,6. 1. Department of Pharmacology, University of Rzeszów, Al. Rejtana 16c, 35-959, Rzeszów, Poland. tutka@umlub.pl. 2. Centre for Innovative Research in Medical and Natural Sciences, University of Rzeszów, Pigonia 1, 35-959, Rzeszów, Poland. tutka@umlub.pl. 3. Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, 20-090, Lublin, Poland. 4. Department of Neurology, School of Medicine, University of California-Davis, Sacramento, CA, USA. 5. Centre of Public Health and Health Promotion, Institute of Rural Health, Jaczewskiego 2, 20-950, Lublin, Poland. 6. Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-950, Lublin, Poland.
Abstract
BACKGROUND: Cytisine (CYT) is a partial agonist of brain α4β2 nicotinic acetylcholine receptors widely used in Central/Eastern Europe for smoking cessation. OBJECTIVES: 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. RESULTS: CYT administered intraperitoneally (i.p.) in a dose of 2 mg kg-1 significantly 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-1 failed 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 ED50 values 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. CONCLUSION: 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.
BACKGROUND:Cytisine (CYT) is a partial agonist of brain α4β2 nicotinic acetylcholine receptors widely used in Central/Eastern Europe for smoking cessation. OBJECTIVES: 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. RESULTS:CYT administered intraperitoneally (i.p.) in a dose of 2 mg kg-1 significantly 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-1 failed 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 ED50 values 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. CONCLUSION: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: Robert West; Witold Zatonski; Magdalena Cedzynska; Dorota Lewandowska; Joanna Pazik; Paul Aveyard; John Stapleton Journal: N Engl J Med Date: 2011-09-29 Impact factor: 91.245
Authors: Jean-Charles Hoda; Wenli Gu; Marc Friedli; Hilary A Phillips; Sonia Bertrand; Stylianos E Antonarakis; David Goudie; Richard Roberts; Ingrid E Scheffer; Carla Marini; Jayesh Patel; Samuel F Berkovic; John C Mulley; Ortrud K Steinlein; Daniel Bertrand Journal: Mol Pharmacol Date: 2008-05-02 Impact factor: 4.436