Forasartan is indicated for the treatment ofhypertension[6] and, similar to other ARBs, it protects the kidneys from kidney blood vessel damage caused by increased kidney blood pressure by blockingrenin–angiotensin system activation.[7]
Forasartan is administered in the active oral form[6] which means that it must go throughfirst 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 ofvascular smooth muscle, and stimulatesaldosterone resulting in sodium reabsorption and increase inblood volume.[9]Smooth muscle contraction occurs due to increased calcium influx through theL-type calcium channels insmooth muscle cells during the plateau component, increasing the intracellular calcium and membrane potential which sustain depolarization and contraction.[10]
Forasartan is a competitive and reversible ARB that competes with the angiotensin II binding site on AT1[11] and relaxesvascular 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 inhibitsL-type calcium channels in the plateau component of thesmooth muscle cells, favoring relaxation of thesmooth muscle.[10] Forasartan also decreasesheart rate by inhibiting the positivechronotropic effect of high frequency preganglionic stimuli.[13]
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 thanlosartan.[6] Research demonstrates that forasartan is also significantly less potent thanlosartan.[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.PMID18691475.
^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.S2CID27624282.
^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.
