Sarpogrelate: Difference between revisions

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+{{Short description|Chemical compound}}
-{{drugbox
+{{cs1 config|name-list-style=vanc|display-authors=6}}
-| IUPAC_name        = 4-[2-(dimethylamino)-1-({2-[2-(3-methoxyphenyl)ethyl]phenoxy}methyl)ethoxy]-4-oxobutanoic acid
+{{Drugbox
-| image             = Sarpogrelate structure.png
+| Verifiedfields = verified
-| width             = 220
+| verifiedrevid = 407721136
-| CAS_number        = 125926-17-2
-| synonyms          = Sarpogrelate, (-)-4-[1-dimethylamino-3-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]propan-2-yl]oxy-4-oxobutanoic acid
+| IUPAC_name = 4-[2-(dimethylamino)-1-({2-[2-(3-methoxyphenyl)ethyl]phenoxy}methyl)ethoxy]-4-oxobutanoic acid
+| image = Sarpogrelate structure.png
-| ATC_prefix        = none
+| width = 250px
-| ATC_suffix        =
-| PubChem           = 5160
+<!--Clinical data-->
-| IUPHAR_ligand = 210
-| DrugBank          =
+| tradename =
+| Drugs.com = {{drugs.com|international|sarpogrelate}}
-| C = 24 | H = 31 | N = 1 | O = 6
+| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
-| molecular_weight  = 429.506 g/mol
+| pregnancy_US = <!-- A / B / C / D / X -->
-| smiles            = CN(C)CC(COC1=CC=CC=C1CCC2=CC(=CC=C2)OC)OC(=O)CCC(=O)O
-| bioavailability   =
+| pregnancy_category =
+| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
-| protein_bound     =
-| metabolism        =
+| legal_CA =
+| legal_UK =
-| elimination_half-life =
-| excretion         =
+| legal_US =
+| legal_status =
-| pregnancy_AU      =  <!-- A / B1 / B2 / B3 / C / D / X -->
-| pregnancy_US      =  <!-- A / B            / C / D / X -->
-| pregnancy_category=
-| legal_AU          =  <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
-| legal_CA          =
-| legal_UK          =
-| legal_US          =
-| legal_status      =
 | routes_of_administration =
+<!--Pharmacokinetic data-->
+| bioavailability =
+| protein_bound =
+| metabolism =
+| elimination_half-life =
+| excretion =
+<!--Identifiers-->
+| CAS_number_Ref = {{cascite|correct|CAS}}
+| CAS_number = 125926-17-2
+| ATC_prefix = None
+| ATC_suffix =
+| PubChem = 5160
+| IUPHAR_ligand = 210
+| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
+| DrugBank =
+| UNII_Ref = {{fdacite|correct|FDA}}
+| UNII = 19P708E787
+| ChEMBL_Ref = {{ebicite|correct|EBI}}
+| ChEMBL = 52939
+| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
+| ChemSpiderID = 4976
+| synonyms = MCI-9042; LS-187,118
+<!--Chemical data-->
+| C=24 | H=31 | N=1 | O=6
+| SMILES = CN(C)CC(COC1=CC=CC=C1CCC2=CC(=CC=C2)OC)OC(=O)CCC(=O)O
+| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
+| StdInChI = 1S/C24H31NO6/c1-25(2)16-21(31-24(28)14-13-23(26)27)17-30-22-10-5-4-8-19(22)12-11-18-7-6-9-20(15-18)29-3/h4-10,15,21H,11-14,16-17H2,1-3H3,(H,26,27)
+| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
+| StdInChIKey = FFYNAVGJSYHHFO-UHFFFAOYSA-N
 }}
-'''Sarpogrelate''' ('''Anplag''', '''MCI-9042''', '''LS-187,118''') is a drug which acts as an [[Antagonist (pharmacology)|antagonist]] at the [[5-HT2A receptor|5HT<sub>2A</sub>]]<ref>Pertz H, Elz S. In-vitro pharmacology of sarpogrelate and the enantiomers of its major metabolite: 5-HT2A receptor specificity, stereoselectivity and modulation of ritanserin-induced depression of 5-HT contractions in rat tail artery. ''Journal of Pharmacy and Pharmacology''. 1995 Apr;47(4):310-6. PMID 7791029</ref><ref>Nishio H, Inoue A, Nakata Y. Binding affinity of sarpogrelate, a new antiplatelet agent, and its metabolite for serotonin receptor subtypes. ''Archives Internationales de Pharmacodynamie et de Therapie''. 1996 Mar-Apr;331(2):189-202. PMID 8937629</ref> and [[5-HT2B receptor|5-HT<sub>2B</sub>]]<ref>Muntasir HA, Hossain M, Bhuiyan MA, Komiyama T, Nakamura T, Ozaki M, Nagatomo T. Identification of a key amino acid of the human 5-HT(2B) serotonin receptor important for sarpogrelate binding. ''Journal of Pharmacological Sciences''. 2007 Jul;104(3):274-7. PMID 17609583</ref> [[Receptor (biochemistry)|receptor]]s. It blocks serotonin-induced platelet aggregation, and has applications in the treatment of many diseases including [[diabetes mellitus]],<ref>Pietraszek MH, Takada Y, Taminato A, Yoshimi T, Watanabe I, Takada A. The effect of MCI-9042 on serotonin-induced platelet aggregation in type 2 diabetes mellitus. ''Thrombosis Research''. 1993 Apr 15;70(2):131-8. PMID 8322284</ref><ref>Ogawa S, Takeuchi K, Sugimura K, Sato C, Fukuda M, Lee R, Ito S, Sato T. The 5-HT2 receptor antagonist sarpogrelate reduces urinary and plasma levels of thromboxane A2 and urinary albumin excretion in non-insulin-dependent diabetes mellitus patients. ''Clinical and Experimental Pharmacology and Physiology''. 1999 May-Jun;26(5-6):461-4. PMID 10386239</ref> [[Buerger's disease]],<ref>Rydzewski A, Urano T, Hachiya T, Kaneko H, Baba S, Takada Y, Takada A. The effect of a 5HT2 receptor antagonist sarpogrelate (MCI-9042) treatment on platelet function in Buerger's disease. ''Thrombosis Research''. 1996 Dec 15;84(6):445-52. PMID 8987165</ref> [[Raynaud's disease]],<ref>Igarashi M, Okuda T, Oh-i T, Koga M. Changes in plasma serotonin concentration and acceleration plethysmograms in patients with Raynaud's phenomenon after long-term treatment with a 5-HT2 receptor antagonist. ''Journal of Dermatology''. 2000 Oct;27(10):643-50. PMID 11092268</ref> [[coronary artery disease]],<ref>Satomura K, Takase B, Hamabe A, Ashida K, Hosaka H, Ohsuzu F, Kurita A. Sarpogrelate, a specific 5HT2-receptor antagonist, improves the coronary microcirculation in coronary artery disease. ''Clinical Cardiology''. 2002 Jan;25(1):28-32. PMID 11808836</ref> [[angina pectoris]],<ref>Kinugawa T, Fujita M, Lee JD, Nakajima H, Hanada H, Miyamoto S. Effectiveness of a novel serotonin blocker, sarpogrelate, for patients with angina pectoris. ''American Heart Journal''. 2002 Aug;144(2):E1. PMID 12177659</ref> and [[atherosclerosis]].<ref>Hayashi T, Sumi D, Matsui-Hirai H, Fukatsu A, Arockia Rani P J, Kano H, Tsunekawa T, Iguchi A. Sarpogrelate HCl, a selective 5-HT2A antagonist, retards the progression of atherosclerosis through a novel mechanism. ''Atherosclerosis''. 2003 May;168(1):23-31. PMID 12732383</ref>
+'''Sarpogrelate''' (former developmental code names '''MCI-9042''', '''LS-187,118''') is a [[drug]] which acts as an [[Antagonist (pharmacology)|antagonist]] at the [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub>]]<ref>{{cite journal | vauthors = Pertz H, Elz S | title = In-vitro pharmacology of sarpogrelate and the enantiomers of its major metabolite: 5-HT2A receptor specificity, stereoselectivity and modulation of ritanserin-induced depression of 5-HT contractions in rat tail artery | journal = The Journal of Pharmacy and Pharmacology | volume = 47 | issue = 4 | pages = 310–6 | date = April 1995 | pmid = 7791029 | doi = 10.1111/j.2042-7158.1995.tb05801.x | s2cid = 25311518 }}</ref><ref>{{cite journal | vauthors = Nishio H, Inoue A, Nakata Y | title = Binding affinity of sarpogrelate, a new antiplatelet agent, and its metabolite for serotonin receptor subtypes | journal = Archives Internationales de Pharmacodynamie et de Therapie | year = 1996 | volume = 331 | issue = 2 | pages = 189–202 | pmid = 8937629 }}</ref> [[5-HT2B receptor|5-HT<sub>2B</sub>]], and [[5-HT2C receptor|5-HT<sub>2C</sub> receptor]]s.<ref name="RashidManivetNishio2003">{{cite journal | vauthors = Rashid M, Manivet P, Nishio H, Pratuangdejkul J, Rajab M, Ishiguro M, Launay JM, Nagatomo T | title = Identification of the binding sites and selectivity of sarpogrelate, a novel 5-HT2 antagonist, to human 5-HT2A, 5-HT2B and 5-HT2C receptor subtypes by molecular modeling | journal = Life Sci | volume = 73 | issue = 2 | pages = 193–207 | date = May 2003 | pmid = 12738034 | doi = 10.1016/s0024-3205(03)00227-3 | url = }}</ref><ref>{{cite journal | vauthors = Muntasir HA, Hossain M, Bhuiyan MA, Komiyama T, Nakamura T, Ozaki M, Nagatomo T | title = Identification of a key amino acid of the human 5-HT(2B) serotonin receptor important for sarpogrelate binding | journal = Journal of Pharmacological Sciences | volume = 104 | issue = 3 | pages = 274–7 | date = July 2007 | pmid = 17609583 | doi = 10.1254/jphs.sc0060241 | doi-access = free }}</ref> However, its [[affinity (pharmacology)|affinities]] for the human 5-HT<sub>2C</sub> and 5-HT<sub>2B</sub> receptors are about one and two orders of magnitude lower than for the human 5-HT<sub>2A</sub> receptor, respectively.<ref name="RashidManivetNishio2003" /> The drug blocks [[serotonin]]-induced [[platelet aggregation]], and has potential applications in the treatment of many diseases including [[diabetes mellitus]],<ref>{{cite journal | vauthors = Pietraszek MH, Takada Y, Taminato A, Yoshimi T, Watanabe I, Takada A | title = The effect of MCI-9042 on serotonin-induced platelet aggregation in type 2 diabetes mellitus | journal = Thrombosis Research | volume = 70 | issue = 2 | pages = 131–8 | date = April 1993 | pmid = 8322284 | doi = 10.1016/0049-3848(93)90154-g }}</ref><ref>{{cite journal | vauthors = Ogawa S, Takeuchi K, Sugimura K, Sato C, Fukuda M, Lee R, Ito S, Sato T | display-authors = 6 | title = The 5-HT2 receptor antagonist sarpogrelate reduces urinary and plasma levels of thromboxane A2 and urinary albumin excretion in non-insulin-dependent diabetes mellitus patients | journal = Clinical and Experimental Pharmacology & Physiology | year = 1999 | volume = 26 | issue = 5–6 | pages = 461–4 | doi = 10.1111/j.1440-1681.1999.03056.x | pmid = 10386239 | s2cid = 31041268 }}</ref> [[Buerger's disease]],<ref>{{cite journal | vauthors = Rydzewski A, Urano T, Hachiya T, Kaneko H, Baba S, Takada Y, Takada A | title = The effect of a 5HT2 receptor antagonist sarpogrelate (MCI-9042) treatment on platelet function in Buerger's disease | journal = Thrombosis Research | volume = 84 | issue = 6 | pages = 445–52 | date = December 1996 | pmid = 8987165 | doi = 10.1016/s0049-3848(96)00212-5 }}</ref> [[Raynaud's disease]],<ref>{{cite journal | vauthors = Igarashi M, Okuda T, Oh-i T, Koga M | title = Changes in plasma serotonin concentration and acceleration plethysmograms in patients with Raynaud's phenomenon after long-term treatment with a 5-HT2 receptor antagonist | journal = The Journal of Dermatology | volume = 27 | issue = 10 | pages = 643–50 | date = October 2000 | pmid = 11092268 | doi = 10.1111/j.1346-8138.2000.tb02246.x | s2cid = 24884976 }}</ref> [[coronary artery disease]],<ref>{{cite journal | vauthors = Satomura K, Takase B, Hamabe A, Ashida K, Hosaka H, Ohsuzu F, Kurita A | title = Sarpogrelate, a specific 5HT2-receptor antagonist, improves the coronary microcirculation in coronary artery disease | journal = Clinical Cardiology | volume = 25 | issue = 1 | pages = 28–32 | date = January 2002 | pmid = 11808836 | doi = 10.1002/clc.4950250108 | pmc = 6654074 }}</ref> [[angina pectoris]],<ref>{{cite journal | vauthors = Kinugawa T, Fujita M, Lee JD, Nakajima H, Hanada H, Miyamoto S | title = Effectiveness of a novel serotonin blocker, sarpogrelate, for patients with angina pectoris | journal = American Heart Journal | volume = 144 | issue = 2 | pages = A1–A6 | date = August 2002 | pmid = 12177659 | doi = 10.1067/mhj.2002.124056 }}</ref> and [[atherosclerosis]].<ref>{{cite journal | vauthors = Hayashi T, Sumi D, Matsui-Hirai H, Fukatsu A, Arockia Rani PJ, Kano H, Tsunekawa T, Iguchi A | display-authors = 6 | title = Sarpogrelate HCl, a selective 5-HT2A antagonist, retards the progression of atherosclerosis through a novel mechanism | journal = Atherosclerosis | volume = 168 | issue = 1 | pages = 23–31 | date = May 2003 | pmid = 12732383 | doi = 10.1016/s0021-9150(03)00054-6 }}</ref>
+The predicted [[log P]] ([[XLogP3]]) of sarpogrelate is 1.2.<ref name="PubChem">{{cite web | title=Sarpogrelate | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/5160 | access-date=24 November 2024}}</ref> A 2004 review stated that it was unknown whether sarpogrelate crosses the [[blood–brain barrier]].<ref name="SainiTakedaGoyal2004">{{cite journal | vauthors = Saini HK, Takeda N, Goyal RK, Kumamoto H, Arneja AS, Dhalla NS | title = Therapeutic potentials of sarpogrelate in cardiovascular disease | journal = Cardiovasc Drug Rev | volume = 22 | issue = 1 | pages = 27–54 | date = 2004 | pmid = 14978517 | doi = 10.1111/j.1527-3466.2004.tb00130.x | url = }}</ref> However, other papers have stated that sarpogrelate minimally crosses into the brain and hence is [[peripherally selective drug|peripherally selective]].<ref name="HashizumeKawakamiYoshida2007">{{cite journal | vauthors = Hashizume H, Kawakami M, Yoshida M, Okada M, Enyo Y, Inomata Y | title = Sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, attenuates neurogenic pain induced by nucleus pulposus in rats | journal = Spine (Phila Pa 1976) | volume = 32 | issue = 3 | pages = 315–320 | date = February 2007 | pmid = 17268262 | doi = 10.1097/01.brs.0000253601.35732.c1 | url = }}</ref><ref name="ObataSaitoIshizaki2000">{{cite journal | vauthors = Obata H, Saito S, Ishizaki K, Goto F | title = Antinociception in rat by sarpogrelate, a selective 5-HT(2A) receptor antagonist, is peripheral | journal = Eur J Pharmacol | volume = 404 | issue = 1–2 | pages = 95–102 | date = September 2000 | pmid = 10980267 | doi = 10.1016/s0014-2999(00)00522-7 | url = }}</ref><ref name="Nishiyama2005">{{cite journal | vauthors = Nishiyama T | title = Effects of a 5-HT2A receptor antagonist, sarpogrelate on thermal or inflammatory pain | journal = Eur J Pharmacol | volume = 516 | issue = 1 | pages = 18–22 | date = May 2005 | pmid = 15916757 | doi = 10.1016/j.ejphar.2005.04.026 | url = | quote = After oral administration of sarpogrelate to rats, the peak sarpogrelate concentration in the brain and spinal cord was about 2% of the plasma concentration (Komatsu et al., 1991). Thus, sarpogrelate has very low permeability of the blood–brain barrier.}}</ref> Accordingly, a rat study found that peak sarpogrelate levels were 50-fold lower in the brain and spinal cord than in the circulation.<ref name="Nishiyama2005" /><ref name="KomatsuEnjoujiNakai1991">{{cite journal | vauthors = Komatsu T, Enjouji S, Nakai H, Inokuchi T, Iida S | title=Studies on the Metabolic Fate of (.+-.)-2-(Dimethylamino)-1-((o-(m-methoxyphenethyl)-phenoxy)methyl)ethyl hydrogen siccinate hydrochloride (MCI-9042). (II). Absorption, Distribution, Metabolism and Excretion after a Single Administration to Rats. | journal=Drug Metabolism and Pharmacokinetics | volume=6 | issue=3 | date=1991 | issn=0916-1139 | doi=10.2133/dmpk.6.377 | doi-access=free | pages=377–398}}</ref>
-== References ==
-{{reflist}}
+== See also ==
-{{Serotonergics}}
+* [[Cinanserin]]
+* [[Naftidrofuryl]]
+== References ==
-[[Category:5-HT2 antagonists]]
+{{Reflist}}
-[[Category:Phenol ethers]]
-[[Category:Carboxylate esters]]
-[[Category:amines]]
+{{Serotonin receptor modulators}}
-{{pharm-stub}}
+[[Category:3-Methoxyphenyl compounds]]
-[[de:Sarpogrelat]]
+[[Category:Abandoned drugs]]
+[[Category:5-HT2A antagonists]]
+[[Category:5-HT2B antagonists]]
+[[Category:5-HT2C antagonists]]
+[[Category:Carboxylate esters]]
+[[Category:Dimethylamino compounds]]
+[[Category:Peripherally selective drugs]]
+[[Category:Phenol ethers]]
+[[Category:Succinates]]