THE EFFECT OF PROGESTERONE AND ITS METABOLITE 5-ALPHA-PREGNAN-3-ALPHA-OL-20-ONE ON FOCAL EPILEPTIC SEIZURES IN THE CATS VISUAL-CORTEX INVIVO

The acute effects of progesterone and its brain metabolite 5alpha-pregnan-3alpha-ol-20-one (3alpha-OH-DHP) on focal epileptic seizures in the cat's visual cortex was studied in vivo using an unanesthetized cervaux-isole preparation. This model made it possible to study in parallel the effect of the drugs on ictal activity and synaptic transmission. A dose-dependent increase in seizure threshold was observed after i.v. injections of both 3alpha-OH-DHP and progesterone, 3alpha-OH-DHP being about 20 times as potent as the latter. i.v. injections of 3alpha-OH-DHP 1.0 mg/kg increased the median seizure threshold to 265% of baseline. While 3alpha-OH-DHP exerted an immediate effect on seizure thresholds, the maximal effect of progesterone was delayed about 20 min. Concerning the mechanisms underlying the antiepileptic effect. three changes occurred within the effective dose range: (1) a small, but significant reduction in the presynaptic nerve volleys, (2) a reduction in the postsynaptic excitatory field potentials in the dorsal lateral geniculate nucleus and cortex, and (3) an enhanced postsynaptic inhibition. Taken together, these observations point to both pre- and postsynaptic effects, supporting the hypothesis of a barbiturate-like mechanism of action of progesterone and its brain metabolites.