Anticonvulsant, but not antiepileptic, action of valproate on audiogenic seizures in metaphit-treated rats

作者：Stanojlovic Olivera P^*; Hrncic Dragan R; Zivanovic Dragana P; Susic Veselinka T

来源：CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2007, 34(10): 1010-1015.

DOI：10.1111/j.1440-1681.2007.04681.x

• audiogenic seizure
• electroencephalography
• metaphit
• rats
• valproate

1. The blocking effects of valproate (2-propylpentanoic acid), a standard anti-epileptic drug, on metaphit (1-[1-(3-isothiocyanatophenyl)-cyclohexyl]-piperidine)-induced audiogenic seizures as a model of generalized, reflex audiogenic epilepsy in adult Wistar male rats were studied.
Rats were stimulated using an electric bell (100 +/- 3 dB, 5-8 kHz, 60 s) 60 min after i.p. metaphit (10 mg/kg) injection and afterwards at hourly intervals. For power spectra and electroencephalograph (EEG) recordings, three gold-plated screws were implanted into the skull. Different doses of valproate (50, 75 and 100 mg/kg) were injected i.p. into rats with fully developed metaphit seizures after the eighth audiogenic testing.
In metaphit-treated animals, the EEG appeared as polyspikes, spike-wave complexes and sleep-like patterns, whereas the power spectra were increased compared with the corresponding controls.
Valproate reduced the incidence and intensity of convulsions and prolonged the duration of the latency period in a dose-dependent manner 4 h after administration.
The ED50 of valproate in the first hour after injection was 63.19 mg/kg (95% confidence interval 51.37-77.71 mg/kg).
None of the doses of valproate applied eliminated the EEG signs of metaphit-provoked epileptiform activity.
Taken together, these results suggest that all doses of valproate examined acted to suppresse behavioural but not epileptic EEG spiking activity in metaphit-induced seizures.

• 出版日期2007-10