title: Anticonvulsant action of topiramate against motor seizures in developing rats.
abstract: OBJECTIVE
  To study the anticonvulsant action of topiramate (TPM) in developing rats.
  
  
  METHODS
  Motor seizures were elicited by administering pentylenetetrazol (100 mg/kg subcutaneously) in five age groups of Wistar rats (7, 12, 18, 25, and 90 days old). TPM was administered intraperitoneally in doses from 10 to 640 mg/kg 2 hours before pentylenetetrazol. The time course of TPM action was studied in 12- and 25-day-old rats up to 24 hours after the 160-mg/kg dose, and the incidence and pattern of seizures were evaluated.
  
  
  RESULTS
  TPM did not influence minimal seizures (clonus of forelimb and head muscles with preserved righting ability). Generalized tonic-clonic seizures, however, were reliably changed at all developmental stages studied. The tonic phase was suppressed so that the majority of animals exhibited generalized clonic seizures (with a loss of righting reflexes). In addition, the incidence of generalized seizures was decreased after the 20-, 40-, and 80-mg/kg doses in the 7-day-old rat pups. The specific suppression of the tonic phase of generalized seizures was observed up to 12 hours in the 12-day-old rat pups. The same result was obtained over 6 hours after TPM administration in the 25-day-old animals, and with longer intervals the incidence of generalized seizures decreased in this age group.
  
  
  CONCLUSIONS
  TPM exhibits stable anticonvulsant action against the tonic phase of generalized tonic-clonic seizures throughout development. In addition, it suppresses all phases of generalized seizures in 7-day-old rats. The anticonvulsant action of TPM lasted longer in 25-day-old than in 12-day-old rats. The two actions of TPM might be ascribed to two different mechanisms of action.
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague.
authors.forename: R
authors.initials: R
authors.lastname: Haugvicová
authors.forename: H
authors.initials: H
authors.lastname: Kubová
authors.forename: M
authors.initials: M
authors.lastname: Skutová
authors.forename: P
authors.initials: P
authors.lastname: Mares
mesh_terms: D000367:Age Factors; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development*; D004195:Disease Models, Animal; D004829:Epilepsy, Generalized / Q000139:chemically induced* / Q000517:prevention & control*; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced / Q000517:prevention & control; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose; D010433:Pentylenetetrazole