Forasartan
Chemical compound
From Wikipedia, the free encyclopedia
Forasartan, otherwise known as the compound SC-52458, is a nonpeptide angiotensin II receptor antagonist (ARB, AT1 receptor blocker).[2][3][4][5]
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| Other names | SC-52458 |
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| Routes of administration | Oral |
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| Elimination half-life | 1–2 hours |
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| Formula | C23H28N8 |
| Molar mass | 416.533 g·mol−1 |
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Indications
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]
Contraindications
Negative side effects of Forasartan are similar to other ARBs, and include hypotension and hyperkalemia.[8] There are no drug interactions identified with forasartan.[6]
Pharmacology
The angiotensin II receptor, type 1
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]