Interaction of flunarizine with sodium valproate or ethosuximide in gamahydroxybutyrate induced absence seizures in rats.
Sodium valproate(VPA), ethosuximide(ESM), 200 mg/kg ip and flunarizine (FLU) 5 or 10 mg/kg ip were first administered independently to rats in order to study their effects on behavioural and EEG aspects of spike and wave discharges (SWDs) induced by y- hydroxybutyrate (GHB,100 mg/kg ip). GHB treated rats show behavioural changes and concomitant repetitive EEG episodes of 7 to 9 Hz SWDs, mimicking human absence seizures (AS), and can be used as a pharmacological model. The number and duration of SWDs were calculated for 1 hr from the EEG and were parameters for drug evaluation. VPA and ESM at 200 mg/kg, significantly reduced SWD number and duration/hr, while FLU showed significant reduction only at 10 but not at 5 mg/kg. Combination of FLU, 10 mg/kg with either VPA or ESM showed significant reduction of SWD number and duration, suggesting an additive effect of the anti-absence agents with the calcium channel blocker, FLU, on experimental absence seizures in rats.
Subramanyam
K
K
Department of Pharmacology, St John's Medical College, Bangalore, India.
David
J
J
Joseph
T
T
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004347:Drug Interactions; D004357:Drug Synergism; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000188:drug therapy*; D005013:Ethosuximide / Q000627:therapeutic use*; D005444:Flunarizine / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012978:Sodium Oxybate; D014635:Valproic Acid / Q000627:therapeutic use*
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D005013:Ethosuximide; D014635:Valproic Acid; D012978:Sodium Oxybate; D005444:Flunarizine