A novel steroid-like compound F90927 exerting positive-inotropic effects in cardiac muscle

Pignier, Christophe; Keller, Markus; Vié, Bruno; Vacher, Bernard; Santelli, Maurice; Niggli, Ernst; Egger, Marcel; Le Grand, Bruno (2006). A novel steroid-like compound F90927 exerting positive-inotropic effects in cardiac muscle. British journal of pharmacology, 147(7), pp. 772-82. Oxford: Wiley-Blackwell 10.1038/sj.bjp.0706673

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Here we report a novel steroid-like compound F90363, exhibiting positive inotropy in vivo and in vitro in various cardiac muscle preparations. F90363 is a racemic mixture composed of the stereoisomers (-)-F90926 and (+)-F90927. Only F90927 exerted positive inotropy, while F90926 induced a weak negative inotropy, but only at concentrations 10(3) times higher than F90927 and most likely resulting from an unspecific interaction. The rapid time course of the action of F90927 suggested a direct interaction with a cellular target rather than a genomic alteration. We could identify the L-type Ca2+ current I(Ca(L)) as a main target of F90927, while excluding other components of cardiac Ca2+ signalling as potential contributors. In addition, several other signaling pathways known to lead to positive inotropy (e.g. alpha- and beta-adrenergic stimulation, cAMP pathways) could be excluded as targets of F90927. However, vessel contraction and stiffening of the cardiac muscle at high doses (>30 microM, 0.36 mg kg(-1), respectively) prevent the use of F90927 as a candidate for drug development. Since the compound may still find valuable applications in research, the aim of the present study was to identify the cellular target and the mechanism of inotropy of F90927.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology
UniBE Contributor:	Pignier, C, Niggli, Ernst
ISSN:	0007-1188
ISBN:	16474419
Publisher:	Wiley-Blackwell
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:45
Last Modified:	05 Dec 2022 14:14
Publisher DOI:	10.1038/sj.bjp.0706673
PubMed ID:	16474419
Web of Science ID:	000236702000010
URI:	https://boris.unibe.ch/id/eprint/18525 (FactScience: 706)