Fimasartan, a novel angiotensin II receptor antagonist

Kim, Je Hak; Lee, Joo Han; Paik, Soo Heui; Kim, Ji Han; Ha, Yong

doi:10.1007/s12272-012-0700-z

Cited by 48 publications

(24 citation statements)

References 7 publications

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“…Fimasartan, an ARB, has been approved for the treatment of essential hypertension in Korea. In addition to its angiotensin II-blocking effects, fimasartan has shown superior inhibition of the contraction of isolated rabbit thoracic aorta compared with other ARBs, such as losartan and candesartan [29], and has been reported to have protective effects in a porcine model of acute myocardial infarction [30]. Fimasartan was also reported to reduce ischemic cell death when used to treat transient focal ischemia in rats [31], and to prevent unilateral ureteral obstruction-induced apoptosis in mice [32].…”

Section: Discussionmentioning

confidence: 99%

Fimasartan, an angiotensin II receptor antagonist, ameliorates an in vivo zebrafish model of heart failure

Quan

Seok

et al. 2020

Korean J Intern Med

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Background/Aims: Angiotensin II in the failing heart initially helps to maintain cardiac output and blood pressure, but ultimately accelerates its deterioration. In this study, we established a model of arrhythmia-induced heart failure (HF) in zebrafish and investigated the role of renin-angiotensin-aldosterone system (RAAS) modulation by using an angiotensin II type 1 receptor blocker, fimasartan, through the assessment of cellular and physiologic responses, morbidity, and mortality. Methods: HF was induced in zebrafish larvae by exposure to 20 μM terfenadine.Morphologic, physiologic, and functional parameters were assessed in the presence or absence of fimasartan treatment. Results: Zebrafish exposed to terfenadine showed marked dilatation of the ventricle and reduced systolic function. Treatment with terfenadine was associated with 10-fold higher expression of atrial natriuretic peptide (p < 0.001 vs. vehicle), increased p53 mRNA expression, and chromatin fragmentation in the TUNEL assay, all of which were significantly reduced by fimasartan treatment. Moreover, fimasartan improved fractional shortening (terfenadine + fimasartan 16.9% ± 3.1% vs. terfenadine + vehicle 11.4% ± 5.6%, p < 0.05) and blood flow (terfenadine + fimasartan 479.1 ± 124.1 nL/sec vs. terfenadine + vehicle 273.0 ± 109.0 nL/sec, p < 0.05). Finally, treatment with fimasartan remarkably reduced mortality (terfenadine + fimasartan 36.0% vs. terfenadine + vehicle 96.0%, p < 0.001). Conclusions: Fimasartan effectively protected against the progression of HF in zebrafish by improving hemodynamic indices, which improved survival. A reduction in apoptotic cell death and an improvement in hemodynamics may be the mechanisms behind these effects. Further human studies are warranted to evaluate the possible role of fimasartan in the treatment of HF.

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Section: Discussionmentioning

confidence: 99%

Fimasartan, an angiotensin II receptor antagonist, ameliorates an in vivo zebrafish model of heart failure

Quan

Seok

et al. 2020

Korean J Intern Med

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“…Fimasartan is a selective AT1 receptor antagonist, for which the safety, efficacy, and dose-response have been investigated in human and rodent studies (Chi et al, 2013; Kim et al, 2015, 2012). On healthy subjects, fimasartan is well tolerated with single oral doses of 20–480 mg (Chi et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage

Yang

Sun

Kim

et al. 2018

Experimental Neurology

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Nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which is composed of an NLRP3 domain, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC) domain, and procaspase-1, plays an important role in the immune pathophysiology of the secondary damage induced by intracerebral hemorrhage (ICH). This study aims to investigate whether pre-stroke treatment with fimasartan, an angiotensin II receptor blocker, has anti-inflammatory effects on ICH by inhibiting the activation of the NLRP3 inflammasome. Sprague-Dawley rats were divided into five groups: sham, vehicle, low-dose (0.5 mg/kg) and regular-doses (1.0 and 3.0 mg/kg) fimasartan. These rats were treated for 30 days before the induction of collagenase-induced ICH and continuously 3 days after surgery. The mean blood pressure (BP) in the low-dose fimasartan group was not significantly different from that of control, and BP in the regular-dose groups was decreased in a dose-dependent manner. Pretreatment with low-dose fimasartan attenuated ICH-induced edema and improved neurological functions. Activation of the NLRP3/ASC/caspase-1 and the NF-κB pathways after ICH was markedly reduced by low-dose fimasartan. The double immunofluorescence staining of brain cells showed a significant decrease in the co-localization of NLRP3 with Iba1 (microglia marker) positive cells by fimasartan treatment. Cultured microglia cells stimulated by hemolysate demonstrated significant activation of the inflammasome, which was reduced by fimasartan. Pretreatment with a low-dose fimasartan alleviated brain damage after acute ICH by inhibiting the NLRP3 inflammasome without lowering MBP. Our study suggests pre-stroke administration of fimasartan could potentially attenuate ICH-induced secondary brain injury by targeting the inflammasome.

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“…Fimasartan is a selective AT1 receptor antagonist. The concentration that inhibits the binding of [ 125 I]Ang II to the AT 1 receptor from rat adrenal cortex by 50% (IC 50 ) was 0.13 nM, compared with 80.0 nM for losartan [1]. …”

Section: Discussionmentioning

confidence: 99%

“…Moreover, fimasartan, by blocking AT 1 receptors, showed superior inhibitory activity in the contraction of isolated rabbit thoracic aorta compared to other ARBs such as losartan and candesartan [1]. In various animal models including renal hypertensive rats, spontaneously hypertensive rats and Beagle dogs, fimasartan effectively reduced blood pressure in a dose-dependent manner following single or repeated oral and intravenous administration [1].…”

Section: Discussionmentioning

confidence: 99%

“…Fimasartan (BR-A-657; BR-A-657-K; Kanarb®) is a synthetic, nonpeptide, angiotensin II (Ang II) antagonist with an Ang II type 1 (AT 1 ) receptor selectivity, newly developed by Boryung Pharmaceutical Company as an oral treatment for hypertension [1]. It is the eighth drug marketed as a member of the Ang II receptor blocker (ARB) class worldwide [2].…”

Section: Introductionmentioning

confidence: 99%

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Influence of Fimasartan (a Novel AT₁Receptor Blocker) on Catecholamine Release in the Adrenal Medulla of Spontaneously Hypertensive Rats

Lim

Lee

Lim

2013

Korean J Physiol Pharmacol

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The aim of this study was to determine whether fimasartan, a newly developed AT1 receptor blocker, can affect the CA release in the isolated perfused model of the adrenal medulla of spontaneously hypertensive rats (SHRs). Fimasartan (5~50 µM) perfused into an adrenal vein for 90 min produced dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high K+ (56 mM, a direct membrane depolarizer), DMPP (100 µM) and McN-A-343 (100 µM). Fimasartan failed to affect basal CA output. Furthermore, in adrenal glands loaded with fimasartan (15 µM), the CA secretory responses evoked by Bay-K-8644 (10 µM, an activator of L-type Ca2+ channels), cyclopiazonic acid (10 µM, an inhibitor of cytoplasmic Ca2+-ATPase), and veratridine (100 µM, an activator of Na+ channels) as well as by angiotensin II (Ang II, 100 nM), were markedly inhibited. In simultaneous presence of fimasartan (15 µM) and L-NAME (30 µM, an inhibitor of NO synthase), the CA secretory responses evoked by ACh, high K+, DMPP, Ang II, Bay-K-8644, and veratridine was not affected in comparison of data obtained from treatment with fimasartan (15 µM) alone. Also there was no difference in NO release between before and after treatment with fimasartan (15 µM). Collectively, these experimental results suggest that fimasartan inhibits the CA secretion evoked by Ang II, and cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of fimasartan may be mediated by blocking the influx of both Na+ and Ca2+ through their ion channels into the rat adrenomedullary chromaffin cells as well as by inhibiting the Ca2+ release from the cytoplasmic calcium store, which is relevant to AT1 receptor blockade without NO release.

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Fimasartan, a novel angiotensin II receptor antagonist

Cited by 48 publications

References 7 publications

Fimasartan, an angiotensin II receptor antagonist, ameliorates an in vivo zebrafish model of heart failure

Fimasartan, an angiotensin II receptor antagonist, ameliorates an in vivo zebrafish model of heart failure

Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage

Influence of Fimasartan (a Novel AT₁Receptor Blocker) on Catecholamine Release in the Adrenal Medulla of Spontaneously Hypertensive Rats

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Fimasartan, a novel angiotensin II receptor antagonist

Cited by 48 publications

References 7 publications

Fimasartan, an angiotensin II receptor antagonist, ameliorates an in vivo zebrafish model of heart failure

Fimasartan, an angiotensin II receptor antagonist, ameliorates an in vivo zebrafish model of heart failure

Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage

Influence of Fimasartan (a Novel AT1Receptor Blocker) on Catecholamine Release in the Adrenal Medulla of Spontaneously Hypertensive Rats

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Influence of Fimasartan (a Novel AT₁Receptor Blocker) on Catecholamine Release in the Adrenal Medulla of Spontaneously Hypertensive Rats