Pharmacologic profile of TA-606, a novel angiotensin II-receptor antagonist in the rat

Journal of Cardiovascular Pharmacology
Y HashimotoS Murata

Abstract

This study was carried out to characterize a novel angiotensin II-receptor antagonist, TA-606, (3-pentyloxy) carbonyloxymethyl-5-acetyl-2-n-propyl-3-[2'(1H-tetrazole-5-yl) biphenyl-4-yl]methyl-4,5,6,7-tetrahydro imidazo [4,5-c] pyridine-4-carboxylate hydrochloride, which is a newly synthesized prodrug of 606A. In anesthetized rats, 606A inhibited angiotensin II-induced pressor response with a median inhibitory concentration (IC50) of 6 microg/kg, i.v., and was 8 times more potent than EXP3174, an active metabolite of losartan. Bioavailability of TA-606 was 11 times higher than that of 606A in Sprague-Dawley rats, with consistent hypotensive potencies in spontaneously hypertensive rats (SHRs). In conscious renal hypertensive rats (RHRs) and conscious SHRs, TA-606 lowered the blood pressure without any effects on the heart rate, and its effective dose for 30 mm Hg (ED30) values were 0.14 and 0.21 mg/kg, p.o., respectively. The effect of TA-606 lasted > 10 h in both models. Moreover, the effect of TA-606 was approximately 30 and 10 times more potent than those of losartan in RHRs and SHRs, respectively. TA-606 did not affect the blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. TA-606 given for 12 weeks ...Continue Reading

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Citations

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Nov 1, 2003·Japanese Heart Journal·Takeshi KashimuraYoshifusa Aizawa
Dec 9, 2014·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Mohamed Elshakre
Jun 4, 2016·Journal of Molecular Graphics & Modelling·Abdolkarim FarrokhzadehAli Ebrahimi
Dec 16, 2016·Journal of Medicinal Chemistry·Lai WeiYe Fang
Jul 27, 2010·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Luís Miguel Teodoro FrijaMaria Lurdes Santos Cristiano
Mar 11, 2008·Organic & Biomolecular Chemistry·L M T FrijaM L S Cristiano
Jul 14, 2011·Organic & Biomolecular Chemistry·Luís M T FrijaM Lurdes S Cristiano
May 1, 2020·British Journal of Pharmacology·Swayam Prakash SrivastavaDaisuke Koya
Nov 17, 2012·Journal of Atherosclerosis and Thrombosis·Junko HotchiToshiaki Hanafusa
Mar 29, 2007·The Journal of Physical Chemistry. a·Luís M T FrijaR Fausto
Dec 1, 2010·The Journal of Physical Chemistry. a·A IsmaelA Gómez-Zavaglia
Jul 13, 2006·The Journal of Physical Chemistry. a·A Gómez-ZavagliaR Fausto

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