JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kokate, T. G.
Right arrow Articles by Rogawski, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kokate, T. G.
Right arrow Articles by Rogawski, M. A.

Vol. 288, Issue 2, 679-684, February 1999

Finasteride, a 5alpha -Reductase Inhibitor, Blocks the Anticonvulsant Activity of Progesterone in Mice

Tushar G. Kokate, Melissa K. Banks, Tamika Magee, Shun-Ichi Yamaguchi and Michael A. Rogawski

Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland

Progesterone is an effective anticonvulsant against pentylenetetrazol (PTZ) seizures. This action is hypothesized to require the metabolic conversion of progesterone to the gamma -aminobutyric acidA receptor potentiating neuroactive steroid allopregnanolone by 5alpha -reductase isoenzymes followed by 3alpha -hydroxy oxidoreduction. We evaluated this possibility using the competitive 5alpha -reductase inhibitor finasteride. Progesterone (50-200 mg/kg, i.p.) protected mice against PTZ-induced seizures in a dose-dependent manner (ED50, 94 mg/kg). Pretreatment with finasteride (50-300 mg/kg, i.p.) produced a dose-dependent (ED50, 146 mg/kg) reversal of the protective effects of progesterone (2 × ED50 dose = 188 mg/kg). In contrast, finasteride (up to 300 mg/kg) failed to affect the anticonvulsant activity of allopregnanolone (10-30 mg/kg, i.p.; ED50, 12 mg/kg). Finasteride (up to 300 mg/kg) did not block the protective effect of high doses of progesterone (250-350 mg/kg) on tonic hindlimb extension in the maximal electroshock seizure test (progesterone ED50, 235 mg/kg). The anticonvulsant activity of progesterone against PTZ-induced seizures can be blocked by 5alpha -reductase inhibition, providing strong evidence that the anticonvulsant effect of the steroid in this model is mediated by its active metabolite allopregnanolone.

0022-3565/99/2882-0679$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Neurosci.Home page
C. Sun, Z. Mtchedlishvili, A. Erisir, and J. Kapur
Diminished Neurosteroid Sensitivity of Synaptic Inhibition and Altered Location of the {alpha}4 Subunit of GABAA Receptors in an Animal Model of Epilepsy
J. Neurosci., November 14, 2007; 27(46): 12641 - 12650.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. Maguire and I. Mody
Neurosteroid Synthesis-Mediated Regulation of GABAA Receptors: Relevance to the Ovarian Cycle and Stress
J. Neurosci., February 28, 2007; 27(9): 2155 - 2162.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. S. Reddy, D. C. Castaneda, B. W. O'Malley, and M. A. Rogawski
Anticonvulsant Activity of Progesterone and Neurosteroids in Progesterone Receptor Knockout Mice
J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 230 - 239.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
F di Michele, M Verdecchia, M Dorofeeva, L Costamagna, G Bernardi, P Curatolo, and E Romeo
GABAA receptor active steroids are altered in epilepsy patients with tuberous sclerosis
J. Neurol. Neurosurg. Psychiatry, May 1, 2003; 74(5): 667 - 670.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
D. S. Reddy and M. A. Rogawski
Stress-Induced Deoxycorticosterone-Derived Neurosteroids Modulate GABAA Receptor Function and Seizure Susceptibility
J. Neurosci., May 1, 2002; 22(9): 3795 - 3805.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
Z. Mtchedlishvili, E. H Bertram, and J. Kapur
Diminished allopregnanolone enhancement of GABAA receptor currents in a rat model of chronic temporal lobe epilepsy
J. Physiol., December 1, 2001; 537(2): 453 - 465.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. S. Reddy and M. A. Rogawski
Chronic Treatment with the Neuroactive Steroid Ganaxolone in the Rat Induces Anticonvulsant Tolerance to Diazepam but Not to Itself
J. Pharmacol. Exp. Ther., December 1, 2000; 295(3): 1241 - 1248.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. S. Reddy and M. A. Rogawski
Enhanced Anticonvulsant Activity of Ganaxolone after Neurosteroid Withdrawal in a Rat Model of Catamenial Epilepsy
J. Pharmacol. Exp. Ther., September 1, 2000; 294(3): 909 - 915.
[Abstract] [Full Text]

Home page
 J. Neurosci.Home page
M. J. VanDoren, D. B. Matthews, G. C. Janis, A. C. Grobin, L. L. Devaud, and A. L. Morrow
Neuroactive Steroid 3alpha -Hydroxy-5alpha -Pregnan-20-One Modulates Electrophysiological and Behavioral Actions of Ethanol
J. Neurosci., March 1, 2000; 20(5): 1982 - 1989.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics.