Effects of the combination of valproate and ethosuximide on spike wave discharges in WAG/Rij rats.
OBJECTIVE
We studied the interaction between valproate (VPA) and ethosuximide (ESM) in diminishing the incidence of absence-like spike-wave discharges (SWDs) in the EEG of WAG/Rij rats.


METHODS
VPA, ESM, their combination and saline were evaluated in 16 rats. The doses of VPA ranged from 0 to 280 mg/kg and the doses of ESM ranged from 0 to 40 mg/kg. For the drug combination, a fixed weight ratio of 7/1 VPA/ESM was used. The incidence of SWDs in the EEG was determined for the period of 15-75 min after injection and compared to the incidence of SWDs prior to injection. The sigmoid-E(max) equation was fitted to the data. Isobolic analysis, on 50% effect, was used to assess the character of the drug interaction.


RESULTS
The parameters for diminishing the incidence of the SWDs were: VPA: ED(50): 121mg/kg; ESM: ED(50): 21.5mg/kg; VPA/ESM: ED(50): 112/16 mg/kg. Isobolic analysis showed that a higher drug load was needed of the combination than of the individual drugs to achieve a 50% reduction of SWDs: factor 1.67; P = 0.012.


CONCLUSIONS
The interaction between valproate and ethosuximide was shown to be infra-additive in diminishing the incidence of SWDs in WAG/Rij rats.
van Rijn
Clementina M
CM
Department of Biological Psychology, Nijmegen Institute for Cognition and Information, University of Nijmegen, Post-box 9104, 6500 HE Nijmegen, The Netherlands. rijn@nici.kun.nl
Sun
Mei Shen
MS
Deckers
Charles L P
CL
Edelbroek
Peter M
PM
Keyser
Antoine
A
Renier
Willy
W
Meinardi
Harry
H
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005013:Ethosuximide / Q000494:pharmacology*; D008297:Male; D051381:Rats; D014635:Valproic Acid / Q000494:pharmacology*
D004338:Drug Combinations; D005013:Ethosuximide; D014635:Valproic Acid