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Only certain antiepileptic drugs prevent seizures induced by pilocarpine.
Brain Res. 1987 Jul; 434(3):281-305.BR

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.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

3607518

Citation

Turski, W A., et al. "Only Certain Antiepileptic Drugs Prevent Seizures Induced By Pilocarpine." Brain Research, vol. 434, no. 3, 1987, pp. 281-305.
Turski WA, Cavalheiro EA, Coimbra C, et al. Only certain antiepileptic drugs prevent seizures induced by pilocarpine. Brain Res. 1987;434(3):281-305.
Turski, W. A., Cavalheiro, E. A., Coimbra, C., da Penha Berzaghi, M., Ikonomidou-Turski, C., & Turski, L. (1987). Only certain antiepileptic drugs prevent seizures induced by pilocarpine. Brain Research, 434(3), 281-305.
Turski WA, et al. Only Certain Antiepileptic Drugs Prevent Seizures Induced By Pilocarpine. Brain Res. 1987;434(3):281-305. PubMed PMID: 3607518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Only certain antiepileptic drugs prevent seizures induced by pilocarpine. AU - Turski,W A, AU - Cavalheiro,E A, AU - Coimbra,C, AU - da Penha Berzaghi,M, AU - Ikonomidou-Turski,C, AU - Turski,L, PY - 1987/7/1/pubmed PY - 1987/7/1/medline PY - 1987/7/1/entrez SP - 281 EP - 305 JF - Brain research JO - Brain Res. VL - 434 IS - 3 N2 - 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. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/3607518/Only_certain_antiepileptic_drugs_prevent_seizures_induced_by_pilocarpine_ L2 - https://medlineplus.gov/seizures.html DB - PRIME DP - Unbound Medicine ER -