norandrostane

English Journal

A synthetic 18-norsteroid distinguishes between two neuroactive steroid binding sites on GABAA receptors.

Evers AS, Chen ZW, Manion BD, Han M, Jiang X, Darbandi-Tonkabon R, Kable T, Bracamontes J, Zorumski CF, Mennerick S, Steinbach JH, Covey DF.SourceDepartment of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. eversa@wustl.edu
The Journal of pharmacology and experimental therapeutics.J Pharmacol Exp Ther.2010 May;333(2):404-13. Epub 2010 Feb 2.
In the absence of GABA, neuroactive steroids that enhance GABA-mediated currents modulate binding of [35S]t-butylbicyclophosphorothionate in a biphasic manner, with enhancement of binding at low concentrations (site NS1) and inhibition at higher concentrations (site NS2). In the current study, compo
PMID 20124410

Hydrogen bonding between the 17beta-substituent of a neurosteroid and the GABA(A) receptor is not obligatory for channel potentiation.

Li P, Bandyopadhyaya AK, Covey DF, Steinbach JH, Akk G.SourceDepartment of Anesthesiology, Washington University in St Louis, St Louis, MO 63110, USA.
British journal of pharmacology.Br J Pharmacol.2009 Nov;158(5):1322-9. Epub 2009 Aug 20.
BACKGROUND AND PURPOSE: Potentiating neurosteroids are some of the most efficacious modulators of the mammalian GABA(A) receptor. One of the crucial interactions may be between the C20 ketone group (D-ring substituent at C17) of the neurosteroid, and the N407 and Y410 residues in the M4 domain of th
PMID 19702782