Forasartan is indicated for the treatment of
hypertension[6] and, similar to other ARBs, it protects the kidneys from kidney blood vessel damage caused by increased kidney blood pressure by blocking
renin–angiotensin system activation.[7]
Administration
Forasartan is administered in the active oral form [6] which means that it must go through
first pass metabolism in the liver. The dose administered ranges between 150 mg-200 mg daily.[6] Increasing to more than 200 mg daily does not offer significantly greater AT1 receptor inhibition.[6] Forasartan is absorbed quickly in the GI, and within an hour it becomes significantly biologically active.[6] Peak plasma concentrations of the drug are reached within one hour.[6]
Angiotensin II binds to AT1 receptors, increases contraction of
vascular smooth muscle, and stimulates
aldosterone resulting in sodium reabsorption and increase in
blood volume.[9]Smooth muscle contraction occurs due to increased calcium influx through the
L-type calcium channels in
smooth muscle cells during the plateau component, increasing the intracellular calcium and membrane potential which sustain depolarization and contraction.[10]
Effects
Forasartan is a competitive and reversible ARB that competes with the angiotensin II binding site on AT1[11] and relaxes
vascular smooth muscle,[10] resulting in decreased blood pressure. Forasartan has a high affinity for the AT1 receptor (
IC50=2.9 +/- 0.1nM).[12] In dogs, it was found to block the pressor response of Angiotensin II with maximal inhibition, 91%.[10] Forasartan administration selectively inhibits
L-type calcium channels in the plateau component of the
smooth muscle cells, favoring relaxation of the
smooth muscle.[10] Forasartan also decreases
heart rate by inhibiting the positive
chronotropic effect of high frequency preganglionic stimuli.[13]
Scarce use
Even though experiments have been conducted on rabbits,[6] guinea pigs,[10] dogs [14] and humans,[6][13] forasartan is not a popular drug of choice for hypertension due to its short duration of action; forasartan is less effective than
losartan.[6] Research demonstrates that forasartan is also significantly less potent than
losartan.[6]
^Ram CV (August 2008). "Angiotensin receptor blockers: current status and future prospects". The American Journal of Medicine. 121 (8): 656–663.
doi:
10.1016/j.amjmed.2008.02.038.
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^Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S (April 2007). "Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology". Clinical Science. 112 (8): 417–428.
doi:
10.1042/cs20060342.
PMID17346243.
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^
abcdeUsune S, Furukawa T (October 1996). "Effects of SC-52458, a new nonpeptide angiotensin II receptor antagonist, on increase in cytoplasmic Ca2+ concentrations and contraction induced by angiotensin II and K(+)-depolarization in guinea-pig taenia coli". General Pharmacology. 27 (7): 1179–1185.
doi:
10.1016/s0306-3623(96)00058-4.
PMID8981065.
^Olins GM, Chen ST, McMahon EG, Palomo MA, Reitz DB (January 1995). "Elucidation of the insurmountable nature of an angiotensin receptor antagonist, SC-54629". Molecular Pharmacology. 47 (1): 115–120.
PMID7838120.