Deoxycorticosterone's anticonvulsant effects in infant rats are blocked by finasteride, but not by indomethacin

Experimental Neurology
Claudia Perez-CruzW M Burnham

Abstract

Deoxycorticosterone (DOC) is a steroid hormone that suppresses seizures in both humans and animals. At higher doses, DOC's anticonvulsant actions are accompanied by sedation and ataxia. The mechanism of DOC's anticonvulsant actions is not known, although it has been suggested that they may relate to DOC's secondary metabolite 3-alpha-5-alpha-tetrahydrodeoxycorticosterone (THDOC). The present study was designed to study the relation of DOC's anticonvulsant actions to its primary and secondary metabolites in 15-day-old rats. It was found that DOC's anticonvulsant and ataxic effects were suppressed by finasteride, which blocks the formation of DOC's primary metabolite, 3-alpha-5-alpha-dehydrodeoxycorticosterone (DHDOC). They were not suppressed by indomethacin (INDO), which blocks the conversion of DHDOC into THDOC. The direct anticonvulsant effects of DHDOC and THDOC were also tested. DHDOC and THDOC were both potent anticonvulsants in 15-day old rats. Both also caused ataxia at high doses. DHDOC had a therapeutic index (TI) of 3.2, however, which was better than either DOC (TI = 1.2) or THDOC (TI = 1.5). It appears that DOC itself is not anticonvulsant, but that its anticonvulsant effects may relate to both its primary and secon...Continue Reading

References

Nov 1, 1992·Naunyn-Schmiedeberg's Archives of Pharmacology·L VelisekR Schickerova
Jul 1, 1989·Brain Research. Brain Research Reviews·R S Fisher
Jul 1, 1994·The Journal of Steroid Biochemistry and Molecular Biology·K C ChengK N Qin
Jun 1, 1993·Biochemistry·B FallerH Nick
Apr 1, 1997·The Journal of Steroid Biochemistry and Molecular Biology·B AzzolinaG S Harris
Jun 27, 1998·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·R KaminskiS J Czuczwar
Jan 6, 2000·The Journal of Steroid Biochemistry and Molecular Biology·W P EechauteJ M Kaufman
Dec 22, 2000·Pharmacology, Biochemistry, and Behavior·A I CzłonkowskaA Płaźnik
Feb 28, 2002·The Journal of Steroid Biochemistry and Molecular Biology·C Q GaoW P Eechaute
May 16, 2002·Experimental Neurology·Heather E EdwardsW McIntyre Burnham
Mar 10, 1951·Journal of the American Medical Association·R B AIRD, G S GORDAN

❮ Previous
Next ❯

Citations

Dec 5, 2008·Epilepsia·Marian Joëls
Jan 12, 2021·Neuroscience Letters·Trina BasuJay A Salpekar
Oct 30, 2020·Frontiers in Endocrinology·Barbara MiziakStanisław J Czuczwar

❮ Previous
Next ❯

Related Concepts

Related Feeds

Ataxia

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxias (MDS)

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.