Effects of the neuroleptanalgesic fentanyl-fluanisone (Hypnorm) on spike-wave discharges in epileptic rats

Effects of fentanyl-fluanisone (Hypnorm), a combination often used as a neuroleptanalgesic and anaesthetic, were investigated on spike-wave discharges of epileptic WAG/Rij rats. Fentanyl-fluanisone has stimulating effects on the amount of spike-wave discharges, but not in a dose-dependent manner. A low dose of 0.01 mg/kg fentanyl with 0.5 mg/kg fluanisone causes a large increase in epileptic activity. This effect is larger than with a middle dose of 0.1 mg/kg fentanyl and 5 mg/kg fluanisone and much larger than with a high dose of 0.2 mg/kg fentanyl with 10 mg/kg fluanisone. The last two doses cause a prolonged anaesthetic state in rats. The frequency of the spikes in the spike-wave discharges was decreased by the mixture of fentanyl-fluanisone; this decrease was dose-dependent. Administration of fentanyl alone in the same doses as in the combination abolishes spike-wave activity during the anaesthetic phase but causes a moderate increase after this phase. It also causes a lowering in spike frequency, which is of the same order as with fentanyl-fluanisone. The mechanisms of action of fentanyl are not completely clear, but the opposite effects of mu- and kappa-opioid receptors on spike-wave discharges may play a role in this biphasic effect. Fluanisone alone in the same doses as in the mixture induces a large dose-dependent increase in spike-wave activity, with only a small effect on spike frequency. This might be caused by the antagonistic action of this drug at dopamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)