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Finasteride inhibits the progesterone-induced spike-wave discharges in a genetic model of absence epilepsy. 2003

Gilles van Luijtelaar, and Bogusława Budziszewska, and Magdalena Tetich, and Władysław Lasoń
NICI, Biological Psychology, University of Nijmegen, The Netherlands. luijtelaar@nici.kun.nl

Previously, it was found that progesterone aggravates spike-wave discharges (SWD) in WAG/Rij rats in a nongenomic way. In order to elucidate whether the regulatory effect of progesterone depends on its conversion to allopregnanolone, the effect of finasteride, a 5alpha-reductase inhibitor, on progesterone-induced increase in SWD was studied in the same model for absence epilepsy. Progesterone (10 and 20 mg/kg ip) dose-dependently increased the number of SWD (by 54% and 97%, respectively) during the first hour postinjection. Pretreatment of rats with finasteride (50 mg/kg sc) blocked the progesterone-induced enhancement of SWD. Finasteride alone had no effect on the number of SWD, up to 24 h following its administration. It is concluded that finasteride blocked the progesterone-induced increase in SWD, which indicates that this action of progesterone is mediated by its neuroactive metabolite allopregnanolone.

UI MeSH Term Description Entries
D008297 Male Males
D011374 Progesterone The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS. Pregnenedione,Progesterone, (13 alpha,17 alpha)-(+-)-Isomer,Progesterone, (17 alpha)-Isomer,Progesterone, (9 beta,10 alpha)-Isomer
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D004832 Epilepsy, Absence A seizure disorder usually occurring in childhood characterized by rhythmic electrical brain discharges of generalized onset. Clinical features include a sudden cessation of ongoing activity usually without loss of postural tone. Rhythmic blinking of the eyelids or lip smacking frequently accompanies the SEIZURES. The usual duration is 5-10 seconds, and multiple episodes may occur daily. Juvenile absence epilepsy is characterized by the juvenile onset of absence seizures and an increased incidence of myoclonus and tonic-clonic seizures. (Menkes, Textbook of Child Neurology, 5th ed, p736) Akinetic Petit Mal,Epilepsy, Minor,Petit Mal Epilepsy,Pyknolepsy,Absence Seizure Disorder,Childhood Absence Epilepsy,Epilepsy Juvenile Absence,Epilepsy, Absence, Atypical,Epilepsy, Petit Mal,Juvenile Absence Epilepsy,Pykno-Epilepsy,Seizure Disorder, Absence,Absence Epilepsy,Absence Epilepsy, Childhood,Absence Epilepsy, Juvenile,Absence Seizure Disorders,Epilepsy, Childhood Absence,Epilepsy, Juvenile Absence,Minor Epilepsy,Petit Mal, Akinetic,Pykno Epilepsy,Pyknolepsies,Seizure Disorders, Absence
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013741 3-Oxo-5-alpha-Steroid 4-Dehydrogenase An enzyme that catalyzes the reduction of TESTOSTERONE to 5-ALPHA DIHYDROTESTOSTERONE. 3-Keto-5-alpha-Steroid delta-4-Dehydrogenase,5-alpha-Reductase, Testosterone,Testosterone 5-alpha-Reductase,Testosterone delta-4-5-alpha-Reductase,3-oxo-5 alpha-Steroid 4-Dehydrogenase (NADP+),3-oxo-5alpha-Steroid 4-Dehydrogenase (NADP+),4-Ene-3-Oxosteroid-5alpha-Reductase,4-Ene-5-alpha-Reductase,NADH-5-alpha-Reductase,NADPH delta(4)-3-Ketosteroid 5 alpha-Oxidoreductase,Steroid 5-alpha-Reductase,Steroid 5Alpha Reductase,Steroid delta-4-5-alpha Reductase,delta 4-3-keto Steroid 5 alpha-Oxidoreductase,delta(4)-3-Ketosteroid-5alpha-Reductase,delta4-3-ketosteroid 5alpha-Oxidoreductase,3 Keto 5 alpha Steroid delta 4 Dehydrogenase,3 Oxo 5 alpha Steroid 4 Dehydrogenase,4 Ene 3 Oxosteroid 5alpha Reductase,4 Ene 5 alpha Reductase,5 alpha Reductase, Testosterone,5-alpha-Reductase, Steroid,5Alpha Reductase, Steroid,5alpha-Oxidoreductase, delta4-3-ketosteroid,NADH 5 alpha Reductase,Reductase, Steroid 5Alpha,Reductase, Steroid delta-4-5-alpha,Steroid 5 alpha Reductase,Steroid delta 4 5 alpha Reductase,Testosterone 5 alpha Reductase,Testosterone delta 4 5 alpha Reductase,delta 4 3 keto Steroid 5 alpha Oxidoreductase,delta-4-5-alpha Reductase, Steroid,delta-4-5-alpha-Reductase, Testosterone,delta-4-Dehydrogenase, 3-Keto-5-alpha-Steroid,delta4 3 ketosteroid 5alpha Oxidoreductase
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D058891 5-alpha Reductase Inhibitors Drugs that inhibit 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE. They are commonly used to reduce the production of DIHYDROTESTOSTERONE. 3-Oxo-5-alpha-Steroid 4-Dehydrogenase Inhibitor,5-alpha Reductase Inhibitor,Steroid 5-alpha-Reductase Inhibitor,Testosterone 5-alpha-Reductase Inhibitor,3-Oxo-5-alpha-Steroid 4-Dehydrogenase Inhibitors,Steroid 5-alpha-Reductase Inhibitors,Testosterone 5-alpha-Reductase Inhibitors,3 Oxo 5 alpha Steroid 4 Dehydrogenase Inhibitor,3 Oxo 5 alpha Steroid 4 Dehydrogenase Inhibitors,4-Dehydrogenase Inhibitor, 3-Oxo-5-alpha-Steroid,4-Dehydrogenase Inhibitors, 3-Oxo-5-alpha-Steroid,5 alpha Reductase Inhibitor,5 alpha Reductase Inhibitors,5-alpha-Reductase Inhibitor, Steroid,5-alpha-Reductase Inhibitor, Testosterone,5-alpha-Reductase Inhibitors, Steroid,5-alpha-Reductase Inhibitors, Testosterone,Inhibitor, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase,Inhibitor, 5-alpha Reductase,Inhibitor, Steroid 5-alpha-Reductase,Inhibitor, Testosterone 5-alpha-Reductase,Inhibitors, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase,Inhibitors, 5-alpha Reductase,Inhibitors, Steroid 5-alpha-Reductase,Inhibitors, Testosterone 5-alpha-Reductase,Reductase Inhibitor, 5-alpha,Reductase Inhibitors, 5-alpha,Steroid 5 alpha Reductase Inhibitor,Steroid 5 alpha Reductase Inhibitors,Testosterone 5 alpha Reductase Inhibitor,Testosterone 5 alpha Reductase Inhibitors

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