PP98 Inf 44.Pdf
0022-3565/97/2803-1284$03.00/0 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 280, No. 3 Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. JPET 280:1284–1295, 1997 Characterization of the Anticonvulsant Properties of Ganaxolone (CCD 1042; 3a-Hydroxy-3b-methyl-5a-pregnan- 20-one), a Selective, High-Affinity, Steroid Modulator of the g-Aminobutyric AcidA Receptor RICHARD B. CARTER, PAUL L. WOOD, SCOTT WIELAND, JON E. HAWKINSON, DELIA BELELLI, JEREMY J. LAMBERT, H. STEVE WHITE, HAROLD H. WOLF, SEID MIRSADEGHI, S. HASAN TAHIR, MICHAEL B. BOLGER, NANCY C. LAN and KELVIN W. GEE Departments of Pharmacology (R.B.C., P.L.W., S.W., J.E.H.) and Medicinal Chemistry (S.M., S.H.T., N.C.L.), CoCensys, Inc., Irvine, California; Department of Pharmacology, University of Dundee, Scotland (D.B., J.J.L.); Anticonvulsant Screening Program, Department of Pharmacology, University of Utah, Salt Lake City, Utah (H.S.W., H.H.W.); School of Pharmacy, University of Southern California, Los Angeles, California (M.B.B.); and Department of Pharmacology, College of Medicine, University of California, Irvine, California (K.W.G.) Accepted for publication November 14, 1996 ABSTRACT Ganaxolone (CCD 1042) is a 3b-methyl-substituted analog of mg/kg i.p.) in mice. Although ganaxolone effectively blocked the endogenous neuroactive steroid 3a-hydroxy-5a-pregnan- tonic seizures induced by maximal electroshock in mice (ED50 20-one. Ganaxolone inhibited binding of the g-aminobutyric of 29.7 mg/kg i.p.), it did so only at doses that produced ataxia 35 acid (GABA)A receptor-chloride channel ligand t-[ S]butylbicy- on the Rotorod (TD50 of 33.4 mg/kg i.p.).
[Show full text]