Evaluation of in vivo interactions in mice between flurazepam and two neuroactive steroids

Pharmacology, Biochemistry, and Behavior
S I DeutschJ Mastropaolo

Abstract

The development of neuroactive steroids as anticonvulsant medications may be useful both as a primary treatment and as an adjuvant to other anticonvulsants. They may be limited, however, by sedative and ataxic side effects. In the current study, 3 alpha-hydroxy-5 beta-pregnan-20-one and alfaxalone, two prototypic neuroactive steroids, were shown to potentiate the ability of flurazepam to antagonize electrically precipitated tonic hindlimb extension in mice at doses that by themselves had little antiseizure efficacy. While alfaxalone alone lacked motor incoordinating effects at a dose (18.0 mg/kg) that potentiated the antiseizure efficacy of flurazepam, the same dose of 3 alpha-hydroxy-5 beta-pregnan-20-one possessed both the ability to potentiate flurazepam's anticonvulsant effect and disrupt mouse rotorod performance. The data suggest that allosteric interactions that have been described in vitro between neuroactive steroids and other modulators of the GABAA receptor complex may have relevance for the intact animal. Finally, the data also suggest that neuroactive steroids could be developed as short-lived adjuvant antiseizure medications in certain critical situations (e.g., medication-refractory status epilepticus). However, ...Continue Reading

References

Oct 1, 1992·Clinical Neuropharmacology·S I DeutschA Hitri
Sep 1, 1995·Trends in Pharmacological Sciences·J J LambertJ A Peters
Apr 1, 1994·Pharmacology, Biochemistry, and Behavior·S I DeutschA Hitri
Dec 1, 1993·Pharmacology, Biochemistry, and Behavior·S I Deutsch, J Mastropaolo

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Citations

Aug 7, 2002·European Journal of Pharmacology·Kinga K BorowiczStanisław J Czuczwar
Oct 6, 2005·Alcoholism, Clinical and Experimental Research·Brett C Ginsburg, R J Lamb

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