The effect of progesterone and its metabolites on the interictal epileptiform discharge in the cat's cerebral cortex

Abstract

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.

Patients with Premenstrual Syndrome Have a Different Sensitivity to a Neuroactive Steroid during the Menstrual Cycle Compared to Control Subjects

“…Administered intravenously in doses of 0.4–0.6 mg/kg, it produces anesthesia of short duration with minimal effects on hemodynamic and respiratory parameters [9]. Pregnanolone has also been reported to have hypnotic activity [10] and basic research on this class of compounds has demonstrated that compounds closely related to pregnanolone possess hypnotic [11], antiepileptic [12] and anxiolytic activity [13]. Brain and plasma levels of allopregnanolone (3α-hydroxy-5α-pregnan-20-one) temporally follow circulating levels of progesterone produced by the corpus luteum [14].…”

Hormonal Effects on Epilepsy in Women

“…Progesterone depresses neuronal firing (I 8), lessens epileptiform discharges, and elevates seizure threshold in most adult animal models with greater effect in female but not in male rats (5,7,19,20).…”

Functional changes in GABAA receptor stimulation during the oestrous cycle of the rat

“…Progesterone, because of its anticonvulsive (Backstrom, 1976;Landgren et al, 1987) and anaesthetic (Seyle, 1942;Meyerson, 1967;Norberg et al, 1987) properties, is of particular interest in this context. The central nervous system depression brought about by progesterone is thought to be mediated by metabolites, e.g.…”