![]() | |
Clinical data | |
---|---|
Other names | SC-52458 |
Pregnancy category |
|
Routes of administration | Oral |
ATC code | |
Legal status | |
Legal status |
|
Pharmacokinetic data | |
Elimination half-life | 1–2 hours |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
Chemical and physical data | |
Formula | C23H28N8 |
Molar mass | 416.533 g·mol−1 |
3D model (JSmol) | |
| |
|
Forasartan, otherwise known as the compound SC-52458, is a nonpeptide angiotensin II receptor antagonist (ARB, AT1 receptor blocker). [2] [3] [4] [5]
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]
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]
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]
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]
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]
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]