Only certain antiepileptic drugs prevent seizures induced by pilocarpine |
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| Authors: | Waldemar A. Turski Esper A. Cavalheiro Cicero Coimbra Maria da Penha Berzaghi Chrysanthy Ikonomidou-Turski Lechoslaw Turski |
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| Affiliation: | 1. Hospital Universitario y Politécnico La Fe, Valencia, Spain;2. Hospital Universitario Puerta de Hierro, Madrid, Spain;3. Hospital General Universitario, Valencia, Spain;4. Hospital Universitario Gregorio Marañón, Madrid, Spain;5. Hospital Universitari Vall d''Hebrón, Barcelona, Spain;6. Centro Neurologia Avanzada, Sevilla, Spain;7. Hospital Universitario Miguel Servet, Zaragoza, Spain;8. Hospital Universitari Lozano Blesa, Zaragoza, Spain;9. Hospital Universitario Donostia, San Sebastian, Spain;10. Hospital Arnau de Vilanova, Valencia, Spain;11. Hospital Universitario Alvaro Cunqueiro, Vigo, Spain;12. Hospital Universitari Virgen de las Nieves, Granada, Spain;13. Complejo Hospitalario Universitario Santiago, Santiago, Spain;14. Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain;15. Hospital Universitario Infanta Sofia, Madrid, Spain;p. Hospital Universitario Doctor Peset, Valencia, Spain;q. Complejo Hospitalario Torrecárdenas, Almeria, Spain;r. Hospital Verge de la Cinta, Tortosa, Spain;1. Research Department, Neuropsychopharmacology Unit, Albacete General Hospital, 37 Hermanos Falcó Street, Albacete E-02006, Spain;2. Department of Genetics, Faculty of Medicine, University of Castilla-La Mancha, 14 Almansa Street, Albacete E-02006, Spain;3. INCYL, University of Salamanca, 1 Pintor Gallego Street, Salamanca E-37007, Spain;1. Department of Psychiatry, Tokyo Women''s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan;2. Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan;3. Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan;4. Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan |
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| Abstract: | Seizures produced in rats by systemically administered pilocarpine (PILO) provide a model for studying the generation and spread of convulsive activity in the forebrain. PILO, 380 mg/kg, induces a sequence of behavioral and electroencephalographic alterations indicative of motor limbic seizures and status epilepticus which is followed by widespread damage to the limbic forebrain resembling that occurring subsequent to prolonged intractable seizures in humans. The present study was undertaken to determine whether clinically utilized antiepileptic drugs share an ability to suppress seizures and brain damage elicited by PILO in rats. Clonazepam, ED50 0.35 mg/kg (0.25–0.49), phenobarbital, 23.4 mg/kg (18.5–29.6), and valproic acid, 286 mg/kg (202–405), prevented the buildup of limbic seizures and protected against seizure-related brain damage. Pretreatment with trimethadione, 179 mg/kg (116–277), resulted in a moderate protection against PILO-induced seizures, whereas carbamazepine, 10–50 mg/kg, and diphenylhydantoin, 10–200 mg/kg, blocked neither convulsions nor brain damage produced by the drug. Surprisingly, ethosuximide, 196 mg/kg (141–272), and acetazolamide, 505 mg/kg (332–766), both lowered the threshold for seizures induced by PILO and converted a non-convulsant dose of PILO, 200 mg/kg, into a convulsant one. These results indicate that only certain anticonvulsant drugs elevate the threshold for PILO-induced seizures and prevent the occurrence of epilepsy-related brain damage. The resistance of seizures produced by PILO in rats to antiepileptic drugs reaffirms the clinically obvious lack of effective treatments for limbic convulsions. |
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| Keywords: | Pilocarpine Temporal lobe epilepsy Seizure Brain damage Antiepileptic drug |
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