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The antiepileptic effect of progesterone, 5-alpha-pregnane-3,20-dione, 3-alpha-hydroxy-5-alpha-pregnane-20-one, and 3-alpha-hydroxy-5-beta-pregnane-20-one were tested in an experimental animal model, and compared with the effect of clonazepam. The steroids were dissolved in serum from ovariectomized cats. Ovariectomized adult cats were used and spontaneous epileptic discharges were generated by placing small pieces of penicillin-soaked filter papers on the ipsi and contralateral cerebral cortex. The frequency and amplitude of the interictal epileptiform spikes were recorded, and analysed in a computer. The changes in frequency and amplitudes were calculated. The drugs were infused during 20-s periods into one cerebral hemisphere via the ipsilateral lingual artery with speeds of 1.1, 3.4 and 6.3 ml min-1. A penicillin focus on the contralateral hemisphere served as a simultaneous control. Progesterone and clonazepam showed similar inhibitory effects on epileptiform interictal spiking (median reduction of spike frequency 21%, cf. Table I). The 5-alpha-pregnane-3, 20-dione was generally less potent than progesterone (median reduction 9%) and the 5-alpha- and 5-beta-pregnanolones were two to three times more potent than progesterone (54-66% reduction). The latency of the inhibitory effect was 4-10 s measured from the entrance of the infusion into the lingual artery. The depression lasted 10-20 min. It is concluded that the pregnanolones have strong antiepileptic properties. The rapid onset of effect indicates that the steroids may interact with the neuronal function at the membrane or synaptic levels.

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