Chiral investigation of midodrine, a long-acting α-adrenergic stimulating agent

Autor: Nicoletta Desideri, A. Farina, Elena Bossù, M. Palmery, Sabrina Strano, M.G. Quaglia, Enrica Donati
Rok vydání: 2004
Předmět:
Zdroj: Chirality. 16:356-362
ISSN: 0899-0042
DOI: 10.1002/chir.20041
Popis: Midodrine hydrochloride is a peripheral α1-adrenoreceptor agonist that induces venous and arterial vasoconstriction. Midodrine, after oral or intravenous administration, undergoes enzymatic hydrolysis and releases deglymidodrine, a pharmacologically active metabolite. Midodrine and deglymidodrine have a chiral carbon in the 2-position. To investigate the bioactivity of racemates and enantiomers of the drug and metabolite, three chromatographic chiral stationary phases, Chiralcel OD-H, Chiralcel OD-R, and α1-AGP, were evaluated for enantiomeric resolution. Good enantioseparation of midodrine racemate was obtained using the Chiralcel OD-H column. This stationary phase was then used to collect separately the midodrine enantiomers. By alkaline hydrolysis of rac-midodrine and each separated enantiomer, rac-deglymidodrine and its enantiomers were prepared. The control of the enantiomeric purity was carried out by α1-AGP stationary phase, while the hydrolysis of rac-midodrine and its enantiomers was controlled by capillary electrophoresis using trimethyl-β-cyclodextrin as chiral selector. The pharmacological activity of the two racemates and the two enantiomeric pairs was tested in vitro on a strip of rabbit descending thoracic aorta. The tests continued that the activity of the drug and metabolite is due only to the (−)-enantiomer because neither of the (+)-enantiomers is active. Chirality 16:356–362, 2004. ©2004 Wiley-Liss, Inc.
Databáze: OpenAIRE
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