Anticonvulsant profile of the progesterone metabolite 5 alpha-pregnan-3 alpha-ol-20-one.
5 alpha-Pregnan-3 alpha-ol-20-one (3 alpha-OH-DHP) is a naturally occurring metabolite of progesterone that can modulate brain excitability through a specific steroid recognition site on the GABA/benzodiazepine receptor-chloride ionophore complex. The anticonvulsant properties of 3 alpha-OH-DHP were determined using standardized anticonvulsant screening tests in mice. This steroid was found to be effective against metrazol-, (+)-bicuculline- and picrotoxin-induced seizures. The steroid has maximum potency against (+)-bicuculline-induced convulsions and no activity against maximal electroshock and strychnine-induced seizures. These findings support the hypothesis that therapeutically useful anticonvulsant steroids active at the putative steroid recognition site associated with the GABA/benzodiazepine receptor-chloride ionophore complex can be identified.
Belelli
D
D
Division of Biological Sciences, School of Pharmacy, University of Southern California, Los Angeles 90033.
Bolger
M B
MB
Gee
K W
KW
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D006993:Hypnotics and Sedatives; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011278:Pregnanes / Q000494:pharmacology*; D011280:Pregnanolone / Q000494:pharmacology* / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
D000927:Anticonvulsants; D006993:Hypnotics and Sedatives; D011278:Pregnanes; D011280:Pregnanolone