Abstract
Inhibition of brain aminopeptidase A (APA), which converts angiotensin II into angiotensin III, has emerged as a novel antihypertensive treatment, as demonstrated in several experimental animal models. QGC001 (originally named RB150) is a prodrug of the specific and selective APA inhibitor EC33, and as such it is the prototype of a new class of centrally acting antihypertensive agents. Given by the oral route in hypertensive rats, it enters the brain and generates EC33, which blocks the brain renin-angiotensin system activity and normalises blood pressure. The aim of the present study was to evaluate the safety, pharmacokinetics and pharmacodynamic effects of QGC001 in humans. Fifty-six healthy male volunteers were randomly assigned to receive in double-blind and fasted conditions single oral doses of 10, 50, 125, 250, 500, 750, 1,000 and 1,250 mg of QGC001 (n = 6/dose) or placebo (n = 2/dose). We measured plasma and urine concentrations of both QGC001 and EC33 by liquid chromatography-tandem mass spectrometry, plasma renin concentrations (PRC), plasma and free urine aldosterone (PAldo and UAldo), plasma copeptine (PCop), and plasma and urine cortisol (PCort and UCort) concentrations, and supine systolic blood pressure (SBP), d...Continue Reading
References
Apr 3, 1992·Journal of Medicinal Chemistry·M C Fournié-ZaluskiB P Roques
Jun 26, 1992·Journal of Medicinal Chemistry·M C Fournié-ZaluskiB P Roques
Sep 1, 1992·Brain Research. Brain Research Reviews·J W Wright, J W Harding
Jan 1, 1985·Clinical and Experimental Hypertension. Part A, Theory and Practice·N BassoA C Taquini
Aug 26, 1983·Science·D GantenR E Lang
Jun 15, 1995·Circulation·M L LachuriéJ Ménard
Apr 29, 1994·Journal of Medicinal Chemistry·E N ChauvelM C Fournié-Zaluski
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·S ZiniC Llorens-Cortes
Nov 11, 1999·Proceedings of the National Academy of Sciences of the United States of America·A ReauxC Llorens-Cortes
Apr 11, 2001·Trends in Endocrinology and Metabolism : TEM·A ReauxC Llorens-Cortes
Mar 20, 2002·Molecular Pharmacology·Hiroshi UchinoHitoshi Endou
Jun 4, 2002·The Journal of Biological Chemistry·Raphael RozenfeldCatherine Llorens-Cortes
Sep 26, 2003·Journal of Hypertension·Michel AziziJoël Ménard
May 12, 2004·Proceedings of the National Academy of Sciences of the United States of America·Marie-Claude Fournie-ZaluskiCatherine Llorens-Cortes
Jan 13, 2006·Circulation·Thomas ThomUNKNOWN American Heart Association Statistics Committee and Stroke Statistics Subcommittee
Feb 23, 2008·Trends in Endocrinology and Metabolism : TEM·Nils G MorgenthalerMartin W Dünser
Mar 1, 2008·Clinical and Experimental Pharmacology & Physiology·Grégoire Wuerzner, Michel Azizi
Mar 26, 2008·Hypertension·Laurence BodineauCatherine Llorens-Cortes
Apr 16, 2008·Journal of Neurochemistry·Nadia de MotaCatherine Llorens-Cortes
Jul 2, 2010·British Journal of Pharmacology·Terry K W MaYat-Yin Lam
Jul 19, 2011·Progress in Neurobiology·Yannick Marc, Catherine Llorens-Cortes
Sep 29, 2011·High Blood Pressure & Cardiovascular Prevention : the Official Journal of the Italian Society of Hypertension·Massimo VolpeClaudio Borghi
Jun 20, 2012·Hypertension·Yannick MarcCatherine Llorens-Cortes
Dec 15, 2012·Circulation·Alan S GoUNKNOWN American Heart Association Statistics Committee and Stroke Statistics Subcommittee
Citations
Dec 5, 2014·Biologie aujourd'hui·Catherine Llorens-Cortès
Apr 5, 2014·Clinical Science·Ji GaoCatherine Llorens-Cortes
Nov 9, 2016·International Journal of Cardiology·A MascoloA Capuano
May 26, 2017·Expert Opinion on Drug Discovery·Maria Tamargo, Juan Tamargo
Oct 3, 2017·Journal of Hypertension·Yannick MarcCatherine Llorens-Cortes
Apr 28, 2018·Current Opinion in Cardiology·Merrill H StewartHector O Ventura
Mar 15, 2015·Circulation Research·Suzanne Oparil, Roland E Schmieder
Feb 12, 2017·F1000Research·Andrew J FreemanRobert E Widdop
May 23, 2019·Current Hypertension Reports·Mathilde KeckCatherine Llorens-Cortes
Mar 19, 2019·Journal of Hypertension·Michel AziziCatherine Llorens-Cortes
Sep 10, 2019·Hypertension·Michel AziziJean-Sébastien Hulot
Sep 12, 2019·Current Hypertension Reports·Omar AzzamMarkus P Schlaich
Jun 11, 2014·Molecular Pharmacology·Yuanyuan ChenPhilip D Kiser
Apr 20, 2017·International Journal of Hypertension·Takuto NakamuraYusuke Ohya
Mar 4, 2019·Current Hypertension Reports·Merrill H StewartHector O Ventura
Sep 21, 2019·Pharmacological Reviews·Lauren B ArendseEdward D Sturrock
Jul 14, 2016·European Heart Journal·Melvin D LoboAtul Pathak
Sep 15, 2017·Chronobiology International·Germán Domínguez-VíasManuel Ramírez-Sánchez
Dec 4, 2019·Hypertension·Catherine Llorens-Cortes, Rhian M Touyz
Aug 27, 2018·Current Hypertension Reports·Jared Davis, Suzanne Oparil
Apr 18, 2017·F1000Research·Lama Ghazi, Paul Drawz
Nov 11, 2017·Cardiovascular Research·Jiao LuFrans H H Leenen
Dec 15, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Qiannan GaoJun Cai
Feb 2, 2021·Avicenna Journal of Medicine·Sara Abdulrahman AlomarAhmed Abu-Zaid
May 12, 2020·The Canadian Journal of Cardiology·Yannick MarcCatherine Llorens-Cortes
Feb 27, 2015·Journal of the American Chemical Society·Kaushik PanigrahiDavid B Berkowitz
Oct 8, 2020·Cardiology in Review·Jagjit KhoslaWilliam H Frishman