Forasartan

Last updated
Forasartan
Forasartan.svg
Clinical data
Other namesSC-52458
Pregnancy
category
  • Not assigned
Routes of
administration 		Oral
ATC code
Legal status
Legal status
  • Development halted, never marketed [1]
Pharmacokinetic data
Elimination half-life 1–2 hours
Identifiers
  • 5-[(3,5-Dibutyl-1H-1,2,4-triazol-1-yl)methyl]-2-[2-(2H-tetrazol-5-yl)phenyl]pyridine
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)
  • CCCCC1=NN(C(=N1)CCCC)CC2=CN=C(C=C2)C3=CC=CC=C3C4=NNN=N4
  • InChI=1S/C23H28N8/c1-3-5-11-21-25-22(12-6-4-2)31(28-21)16-17-13-14-20(24-15-17)18-9-7-8-10-19(18)23-26-29-30-27-23/h7-10,13-15H,3-6,11-12,16H2,1-2H3,(H,26,27,29,30)
  • Key:YONOBYIBNBCDSJ-UHFFFAOYSA-N

Forasartan, otherwise known as the compound SC-52458, is a nonpeptide angiotensin II receptor antagonist (ARB, AT1 receptor blocker). [2] [3] [4] [5]

Contents

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]

See also

Related Research Articles

<span class="mw-page-title-main">ACE inhibitor</span> Class of medications used primarily to treat high blood pressure

Angiotensin-converting-enzyme inhibitors are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart.

<span class="mw-page-title-main">Angiotensin</span> Group of peptide hormones in mammals

Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrenal cortex to promote sodium retention by the kidneys.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

<span class="mw-page-title-main">Amlodipine</span> Medication against high blood pressure

Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat high blood pressure, coronary artery disease (CAD) and variant angina. It is taken orally.

The angiotensin II receptors, (ATR1) and (ATR2), are a class of G protein-coupled receptors with angiotensin II as their ligands. They are important in the renin–angiotensin system: they are responsible for the signal transduction of the vasoconstricting stimulus of the main effector hormone, angiotensin II.

<span class="mw-page-title-main">Angiotensin II receptor blocker</span> Group of pharmaceuticals that modulate the renin–angiotensin system

Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system.

<span class="mw-page-title-main">Irbesartan</span> Chemical compound

Irbesartan, sold under the brand name Avapro among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination irbesartan/hydrochlorothiazide.

<span class="mw-page-title-main">Telmisartan</span> Angiotensin II receptor antagonist

Telmisartan, sold under the brand name Micardis among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination telmisartan/hydrochlorothiazide, telmisartan/cilnidipine and telmisartan/amlodipine.

<span class="mw-page-title-main">Subfornical organ</span>

The subfornical organ (SFO) is one of the circumventricular organs of the brain. Its name comes from its location on the ventral surface of the fornix near the interventricular foramina, which interconnect the lateral ventricles and the third ventricle. Like all circumventricular organs, the subfornical organ is well-vascularized, and like all circumventricular organs except the subcommissural organ, some SFO capillaries have fenestrations, which increase capillary permeability. The SFO is considered a sensory circumventricular organ because it is responsive to a wide variety of hormones and neurotransmitters, as opposed to secretory circumventricular organs, which are specialized in the release of certain substances.

<span class="mw-page-title-main">Losartan</span> Blood pressure medication

Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin receptor blocker (ARB) family of medication, and is considered protective of the kidneys. Besides hypertension, it is also used in diabetic kidney disease, heart failure, and left ventricular enlargement. It comes as a tablet that is taken by mouth. It may be used alone or in addition to other blood pressure medication. Up to six weeks may be required for the full effects to occur.

<span class="mw-page-title-main">Valsartan</span> Angiotensin II receptor antagonist

Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination valsartan/hydrochlorothiazide, valsartan/amlodipine, valsartan/amlodipine/hydrochlorothiazide, or valsartan/sacubitril.

<span class="mw-page-title-main">Olmesartan</span> Angiotensin II receptor antagonist

Olmesartan, sold under the brand name Benicar among others, is a medication used to treat high blood pressure (hypertension). It is taken by mouth. Versions are available as the combination olmesartan/hydrochlorothiazide and olmesartan/amlodipine.

<span class="mw-page-title-main">Bisoprolol</span> Beta-1 selective adrenenergic blocker medication used to treat cardiovascular diseases

Bisoprolol, sold under the brand name Zebeta among others, is a beta blocker medication used for heart diseases. This includes tachyarrhythmias, high blood pressure, chest pain from not enough blood flow to the heart, and heart failure. It is taken by mouth.

<span class="mw-page-title-main">Adrenergic antagonist</span>

An adrenergic antagonist is a drug that inhibits the function of adrenergic receptors. There are five adrenergic receptors, which are divided into two groups. The first group of receptors are the beta (β) adrenergic receptors. There are β1, β2, and β3 receptors. The second group contains the alpha (α) adrenoreceptors. There are only α1 and α2 receptors. Adrenergic receptors are located near the heart, kidneys, lungs, and gastrointestinal tract. There are also α-adreno receptors that are located on vascular smooth muscle.

<span class="mw-page-title-main">Angiotensin II receptor type 1</span> Protein-coding gene in the species Homo sapiens

Angiotensin II receptor type 1(AT1) is a Gq/11-coupled G protein-coupled receptor (GPCR) and the best characterized angiotensin receptor. It is encoded in humans by the AGTR1 gene. AT1 has vasopressor effects and regulates aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. Angiotensin II receptor blockers are drugs indicated for hypertension, diabetic nephropathy and congestive heart failure.

<span class="mw-page-title-main">Alpha blocker</span> Class of pharmacological agents

Alpha-blockers, also known as α-blockers or α-adrenoreceptor antagonists, are a class of pharmacological agents that act as antagonists on α-adrenergic receptors (α-adrenoceptors).

The angiotensin receptor blockers (ARBs), also called angiotensin (AT1) receptor antagonists or sartans, are a group of antihypertensive drugs that act by blocking the effects of the hormone angiotensin II in the body, thereby lowering blood pressure. Their structure is similar to Ang II and they bind to Ang II receptors as inhibitors, e.g., [T24 from Rhys Healthcare].

<span class="mw-page-title-main">Valsartan/hydrochlorothiazide</span> Chemical compound

Valsartan/hydrochlorothiazide, sold under the brand name Diovan HCT among others, is a medication used to treat high blood pressure when valsartan is not sufficient. It is a combination of valsartan, an angiotensin receptor blocker with hydrochlorothiazide, a diuretic. It is taken by mouth.

<span class="mw-page-title-main">Macitentan</span> Chemical compound

Macitentan, sold under the brand name Opsumit, is an endothelin receptor antagonist (ERA) developed by Actelion and approved for the treatment of pulmonary arterial hypertension (PAH). The other two ERAs marketed as of 2014 are bosentan and ambrisentan. Macitentan is a dual ERA, meaning that it acts as an antagonist of two endothelin (ET) receptor subtypes, ETA and ETB. However, macitentan has a 50-fold increased selectivity for the ETA subtype compared to the ETB subtype. The drug received approval from the U.S. Food and Drug Administration (FDA) on October 13, 2013.

<span class="mw-page-title-main">Fimasartan</span> Chemical compound

Fimasartan is a non-peptide angiotensin II receptor antagonist (ARB) used for the treatment of hypertension and heart failure. Through oral administration, fimasartan blocks angiotensin II receptor type 1 (AT1 receptors), 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.

References

  1. ↑ Bräse S, Banert K (2010). Organic Azides: Syntheses and Applications. New York: Wiley. p. 38. ISBN   978-0-470-51998-1.
  2. ↑ Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, et al. (January 2011). "DrugBank 3.0: a comprehensive resource for 'omics' research on drugs". Nucleic Acids Research. 39 (Database issue): D1035–D1041. doi:10.1093/nar/gkq1126. PMC   3013709 . PMID   21059682.
  3. ↑ Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, et al. (January 2008). "DrugBank: a knowledgebase for drugs, drug actions and drug targets". Nucleic Acids Research. 36 (Database issue): D901–D906. doi:10.1093/nar/gkm958. PMC   2238889 . PMID   18048412.
  4. ↑ Wishart DS, Knox C, Guo AC, Shrivastava S, Hassanali M, Stothard P, et al. (January 2006). "DrugBank: a comprehensive resource for in silico drug discovery and exploration". Nucleic Acids Research. 34 (Database issue): D668–D672. doi:10.1093/nar/gkj067. PMC   1347430 . PMID   16381955.
  5. ↑ Olins GM, Corpus VM, Chen ST, McMahon EG, Palomo MA, McGraw DE, et al. (October 1993). "Pharmacology of SC-52458, an orally active, nonpeptide angiotensin AT1 receptor antagonist". Journal of Cardiovascular Pharmacology. 22 (4): 617–625. doi: 10.1097/00005344-199310000-00016 . PMID   7505365. S2CID   93468.
  6. 1 2 3 4 5 6 7 8 9 10 11 Hagmann M, Nussberger J, Naudin RB, Burns TS, Karim A, Waeber B, Brunner HR (April 1997). "SC-52458, an orally active angiotensin II-receptor antagonist: inhibition of blood pressure response to angiotensin II challenges and pharmacokinetics in normal volunteers". Journal of Cardiovascular Pharmacology. 29 (4): 444–450. doi: 10.1097/00005344-199704000-00003 . PMID   9156352.
  7. ↑ Naik P, Murumkar P, Giridhar R, Yadav MR (December 2010). "Angiotensin II receptor type 1 (AT1) selective nonpeptidic antagonists--a perspective". Bioorganic & Medicinal Chemistry. 18 (24): 8418–8456. doi:10.1016/j.bmc.2010.10.043. PMID   21071232.
  8. ↑ 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. PMID   18691475.
  9. ↑ 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. PMID   17346243. S2CID   27624282.
  10. 1 2 3 4 5 Usune 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. PMID   8981065.
  11. ↑ 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. PMID   7838120.
  12. ↑ Csajka C, Buclin T, Fattinger K, Brunner HR, Biollaz J (2002). "Population pharmacokinetic-pharmacodynamic modelling of angiotensin receptor blockade in healthy volunteers". Clinical Pharmacokinetics. 41 (2): 137–152. doi:10.2165/00003088-200241020-00005. PMID   11888333. S2CID   13185772.
  13. 1 2 Kushiku K, Yamada H, Shibata K, Tokunaga R, Katsuragi T, Furukawa T (January 2001). "Upregulation of immunoreactive angiotensin II release and angiotensinogen mRNA expression by high-frequency preganglionic stimulation at the canine cardiac sympathetic ganglia". Circulation Research. 88 (1): 110–116. doi: 10.1161/01.res.88.1.110 . PMID   11139482.
  14. ↑ McMahon EG, Yang PC, Babler MA, Suleymanov OD, Palomo MA, Olins GM, Cook CS (June 1997). "Effects of SC-52458, an angiotensin AT1 receptor antagonist, in the dog". American Journal of Hypertension. 10 (6): 671–677. doi: 10.1016/s0895-7061(96)00500-6 . PMID   9194514.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.