Fimasartan
Fimasartan is a non-peptide angiotensin II receptor antagonist used for the treatment of hypertension and heart failure. Through oral administration, fimasartan blocks angiotensin II receptor type 1, reducing pro-hypertensive actions of angiotensin II, such as systemic vasoconstriction and water retention by the kidneys. Concurrent administration of fimasartan with diuretic hydrochlorothiazide has shown to be safe in clinical trials. Fimasartan was approved for use in South Korea on September 9, 2010, and is available under the brand name Kanarb through Boryung Pharmaceuticals, who are presently seeking worldwide partnership.
Mechanism of action
Fimasartan acts on the kidney's rennin-angiotensin cascade, which begins when renin release from the kidney causes the breakdown of angiotensinogen into angiotensin I. Angiotensin-converting enzyme then catalyzes the reaction that forms angiotensin II, which acts on AT1 receptors on the blood vessels, heart, and kidneys. On blood vessels, the AT1 receptor is coupled to an intracellular pathway that causes smooth muscle contraction of blood vessels.In blocking the AT1 receptor, fimasartan inhibits vasoconstriction, favouring vasodilation. At the kidney and adrenal gland, AT1 blockage and prevention of aldosterone formation increase excretion of water and salt by the kidneys, which decreases overall blood volume. At the heart, AT1 blockage decreases contractility and the stimulatory effects of the sympathetic nervous system. Collectively, fimasartan leads to a reduction in blood pressure and alleviation of hypertensive symptoms. ARBs like fimasartan have also shown to be protective against stroke, myocardial infarction, and heart failure. Fimasartan has been shown to reduce cardiac hypertrophy, fibrosis, remodelling, and unnecessary cell proliferation via blockage of AT1 activation conceivably through decreased Endothelin 1 production, a result of AT1 activation. Fimastartan can also block TGF-β1 production, which contributes to fibrosis and ventricular damage post-infarct. After ARB administration, mice showed improved prognosis after a myocardial infarction, though further studies still need to be done to assess fimasartan's specific effects on decreasing cardiovascular damage.
Side effects
Side effectsIn clinical trials, fimasartan was well tolerated in all patients. However, higher dosing was accompanied by increased dizziness and headaches in a low number of patients. Other side effects such as diarrhea, syncope, and cold feet were also experienced in a low number of subjects, which all resolved without medical intervention.