| 词条 | Forasartan |
| 释义 |
| drug_name = | IUPAC_name = 5-[(3,5-Dibutyl-1H-1,2,4-triazol-1-yl)methyl]-2-[2-(2H-tetrazol-5-yl)phenyl]pyridine | image = Forasartan.svg | alt = | caption = | tradename = | Drugs.com = | MedlinePlus = | pregnancy_AU = | pregnancy_US = | pregnancy_category= Not assigned | legal_AU = | legal_CA = | legal_UK = | legal_US = | legal_status = Development halted, never marketed[1] | routes_of_administration = Oral | bioavailability = | protein_bound = | metabolism = | elimination_half-life = 1–2 hours | excretion = | CAS_number = 145216-43-9 | ATC_prefix = C09 | ATC_suffix = CA | ATC_supplemental = | PubChem = 132706 | DrugBank = DB01342 | ChemSpiderID = 117146 | UNII = 065F7WPT0B | KEGG = D04243 | ChEBI = 141552 | ChEMBL = 315021 | synonyms = SC-52458 | C=23 |H=28 |N=8 | molecular_weight = 416.522 g·mol−1 | smiles = CCCCC1=NN(C(=N1)CCCC)CC2=CN=C(C=C2)C3=CC=CC=C3C4=NNN=N4 | StdInChI = 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) | StdInChI_comment = | StdInChIKey = 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] IndicationsForasartan 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.[6] AdministrationForasartan 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.[7] Increasing to more than 200 mg daily does not offer significantly greater AT1 receptor inhibition.[7] Forasartan is absorbed quickly in the GI, and within an hour it becomes significantly biologically active.[7] Peak plasma concentrations of the drug are reached within one hour.[7] ContraindicationsNegative side effects of Forasartan are similar to other ARBs, and include hypotension and hyperkalemia.[8] There are no drug interactions identified with forasartan.[7] PharmacologyThe angiotensin II receptor, type 1Angiotensin 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] EffectsForasartan 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 useEven though experiments have been conducted on rabbits,[7] guinea pigs,[10] dogs [14] and humans,[7][13] forasartan is not a popular drug of choice for hypertension due to its short duration of action; forasartan is less effective than losartan.[7] Research demonstrates that forasartan is also significantly less potent than losartan.[7] See also
References1. ^{{cite book |author1=Bräse, Stefan |author2=Banert, Klaus |title=Organic Azides: Syntheses and Applications |publisher=Wiley |location=New York |year=2010 |page=38 |isbn=0-470-51998-3}} {{Angiotensin receptor modulators}}2. ^{{cite journal|last=Knox|first=C|author2=Law V|title=a comprehensive resource for 'omics' research on drugs|journal=Nucleic Acids Res|year=2011|volume=39|series=DrugBank|pages=D1035-41|doi=10.1093/nar/gkq1126|pmid=21059682|pmc=3013709}} 3. ^{{cite journal|last=Wishart|first=DS|author2=Knox C|title=a knowledgebase for drugs, drug actions and drug targets|journal=Nucleic Acids Res|year=2008|volume=36|pages=D901-6|doi=10.1093/nar/gkm958|pmid=18048412|pmc=2238889}} 4. ^{{cite journal|last=Wishart|first=DS|author2=Knox C|title=a comprehensive resource for in silico drug discovery and exploration|journal=Nucleic Acids Res|year=2006|volume=34|pages=D668-72|doi=10.1093/nar/gkj067|pmid=16381955|pmc=1347430}} 5. ^{{cite journal|last=Olins|first=GM|author2=Corpus VM|title=Pharmacology of SC-52458, an orally active, nonpeptide angiotensin AT1 receptor antagonist|journal=Journal of Cardiovascular Pharmacology|year=1993|volume=22|issue=4|pages=617–625|doi=10.1097/00005344-199310000-00016}} 6. ^{{cite journal|last=Naik|first=P|author2=Murumkar P|title=Angiotensin II receptor type 1 (AT1) selective nonpeptidic antagonists—A perspective|journal=Bioorganic & Medicinal Chemistry|year=2010|volume=18|issue=24|pages=8418–8456|doi=10.1016/j.bmc.2010.10.043}} 7. ^1 2 3 4 5 6 7 8 9 10 {{cite journal|last=Hagmann|first=M|author2=Nussberger J|title=an Orally Active Angiotensin II-Receptor Antagonist: Inhibition of Blood Pressure Response to Angiotensin II Challenges and Pharmacokinetics in Normal Volunteers|journal=Journal of Cardiovascular Pharmacology|year=1997|volume=29|issue=4|pages=444–450|doi=10.1097/00005344-199704000-00003}} 8. ^{{cite journal|last=Venkata|first=S|author2=Ram MD|title=Angiotensin Receptor Blockers: Current Status and Future Prospects|journal=The American Journal of Medicine|year=2008|volume=121|issue=8|pages=656–663|doi=10.1016/j.amjmed.2008.02.038}} 9. ^{{cite journal|last=Higuchi|first=S|author2=Ohtsu H|title=Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology|journal=Clinical Science|year=2007|volume=112|issue=8|pages=417–428|doi=10.1042/cs20060342|pmid=17346243}} 10. ^1 2 3 4 {{cite journal|last=Usune|first=S|author2=Furukawa T|title=Effects of SC-52458, a New Nonpeptide Angiotensin II Receptor Antagonist, on Increase in Cytoplasmic Ca 2+ Concentrations and Contraction Induced by Angiotensin II and K+-Depolarization in Guinea-Pig Taenia Coli|journal=General Pharmacology|year=1996|volume=27|issue=7|pages=1179–1185|doi=10.1016/s0306-3623(96)00058-4}} 11. ^{{cite journal|last=Olins|first=GM|author2=Chen ST|title=Elucidation of the Insurmountable Nature of an Angiotensin Receptor|journal=Molecular Pharmacology|year=1995|volume=47|issue=1|pages=115–120}} 12. ^{{cite journal|last=Csajka|first=C|author2=Buclin T|title=Population Pharmacokinetic-Pharmacodynamic Modelling of Angiotensin Receptor Blockade in Healthy Volunteers|journal=Clinical Pharmacokinetics|year=2002|volume=41|issue=2|pages=137–152|doi=10.2165/00003088-200241020-00005}} 13. ^1 {{cite journal|last=Kushiki|first=K|author2=Yamada H|title=Upregulation of Immunoreactive Angiotensin II Release and Angiotensinogen mRNA Expression by High-Frequency Preganglionic Stimulation at the Canine Cardiac Sympathetic Ganglia|journal=Circulation Research|year=2001|volume=88|issue=1|pages=110–116|doi=10.1161/01.res.88.1.110}} 14. ^{{cite journal|last=McMahon|first=EG|author2=Yang PC|title=Effects of SC-52458, an Angiotensin AT1 Receptor Antagonist, in the Dog|journal=American Journal of Hypertension|year=1997|volume=10|issue=6|pages=671–677}} 4 : Angiotensin II receptor antagonists|Tetrazoles|Triazoles|Pyridines |
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