Synergistic anticonvulsant effect of valproic acid and ethosuximide on pentylenetetrazole-induced epileptic phenomena in rats.
The possible synergistic effect of valproic acid and ethosuximide in combination on pentylenetetrazole-induced epilepsy was investigated in rats. Valproic acid and ethosuximide administered intraperitoneally both showed dose-dependent anti-epileptic activity towards pentylenetetrazole-induced myoclonias and tonic-clonic seizures. The valproic acid-ethosuximide combination had a synergistic pharmacological effect. Against myoclonias combined valproic acid-ethosuximide produced a non-significant decrease in the effective dose of both drugs compared with treatment with either drug alone. In the case of tonic-clonic seizures the protective effect against the seizures was significantly increased by combined treatment compared with treatment with either drug alone. Neither plasma concentrations nor any other pharmacokinetic parameters were significantly changed when the same doses of valproic acid and ethosuximide were given, singly or in combination.
Musolino
R
R
Neurological Clinic, University of Messina, Italy.
Gallitto
G
G
De Domenico
P
P
Bonazinga
M M
MM
Sturniolo
R
R
Labate
C
C
Di Perri
R
R
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D005013:Ethosuximide / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology; D014635:Valproic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use*
D005013:Ethosuximide; D014635:Valproic Acid; D010433:Pentylenetetrazole