Sarpogrelate

Chemical compound From Wikipedia, the free encyclopedia

Sarpogrelate (INNTooltip International Nonproprietary Name, JANTooltip Japanese Accepted Name), sold under the brand names Anplag and Sapodifil, is a serotonin 5-HT₂ receptor antagonist which is used in the treatment of arterial occlusive disorders such as peripheral artery disease in Japan, South Korea, and China.^[1]^[2]^[3]^[4] Development in the United States and the European Union was discontinued and it is not available in these regions.^[1]^[3]

Trade namesAnplag; Sapodifil

Other namesMCI-9042; LS-187,118; LS-187118; KW-21027

AHFS/Drugs.comInternational Drug Names

Drug classSerotonin 5-HT₂ receptor antagonist; Serotonin 5-HT_2A receptor antagonist; Anticoagulant; Platelet aggregation inhibitor

Quick facts Clinical data, Trade names ...

Sarpogrelate
Clinical data

Trade names	Anplag; Sapodifil
Other names	MCI-9042; LS-187,118; LS-187118; KW-21027
AHFS/Drugs.com	International Drug Names
Drug class	Serotonin 5-HT₂ receptor antagonist; Serotonin 5-HT_2A receptor antagonist; Anticoagulant; Platelet aggregation inhibitor
ATC code	None
Identifiers
IUPAC name 4-[2-(dimethylamino)-1-({2-[2-(3-methoxyphenyl)ethyl]phenoxy}methyl)ethoxy]-4-oxobutanoic acid
CAS Number	125926-17-2^Y
PubChem CID	5160
IUPHAR/BPS	210
ChemSpider	4976^Y
UNII	19P708E787
ChEMBL	ChEMBL52939^Y
CompTox Dashboard (EPA)	DTXSID7048328
Chemical and physical data
Formula	C₂₄H₃₁NO₆
Molar mass	429.513 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CN(C)CC(COC1=CC=CC=C1CCC2=CC(=CC=C2)OC)OC(=O)CCC(=O)O
InChI InChI=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)^N Key:FFYNAVGJSYHHFO-UHFFFAOYSA-N^N
(verify)

The drug acts as an antagonist at the serotonin 5-HT_2A,^[5]^[6] 5-HT_2B, and 5-HT_2C receptors.^[7]^[8] However, its affinities for the human 5-HT_2C and 5-HT_2B receptors are about one and two orders of magnitude lower than for the human 5-HT_2A receptor, respectively.^[7] The drug blocks serotonin-induced platelet aggregation, and has potential applications in the treatment of many diseases including diabetes mellitus,^[9]^[10] Buerger's disease,^[11] Raynaud's disease,^[12] coronary artery disease,^[13] angina pectoris,^[14] and atherosclerosis.^[15]

The predicted log P (XLogP3) of sarpogrelate is 1.2.^[16] A 2004 review stated that it was unknown whether sarpogrelate crosses the blood–brain barrier.^[17] However, other papers have stated that sarpogrelate minimally crosses into the brain and hence is peripherally selective.^[18]^[19]^[20] Accordingly, a rat study found that peak sarpogrelate levels were 50-fold lower in the brain and spinal cord than in the circulation.^[20]^[21]

References

[1]
"Sarpogrelate". AdisInsight. 12 December 2025. Retrieved 16 January 2026.
[2]
Index Nominum: International Drug Directory. CRC Press. 2004. ISBN 978-3-88763-101-7. Retrieved 16 January 2026.
[3]
Pilowsky PM (21 September 2018). Serotonin: The Mediator that Spans Evolution. Academic Press. ISBN 978-0-12-800584-2. Retrieved 16 January 2026. Sarpogrelate hydrochloride remains on market, albeit limited to circulation in Japan, China, and Korea, with development in the United States and EU discontinued. Sarpogrelate hydrochloride (brand name Anplag) is structurally different from Ketanserin, a feature presumably contributing to its improved receptor subtype selectivity. Although Anplag demonstrated lower bleeding rates compared to those induced with aspirin, trials for use in stroke were discontinued, and Anplag remains contraindicated for patients at increased bleeding risk. Anplag is currently only available for chronic arterial occlusion and has been demonstrated to be particularly effective on the collateral circulation, with its main utility for the treatment of peripheral arterial disease (PAD) [169]. A sustained-release formulation of Sarpogrelate hydrochloride (DP-R202 or Sapodifil SR, once daily) was launched in Korea in May of 2015, again for use in PAD.
[4]
"Sarpogrelate controlled release". AdisInsight. 31 October 2021. Retrieved 16 January 2026.
[5]
Pertz H, Elz S (April 1995). "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". The Journal of Pharmacy and Pharmacology. 47 (4): 310–6. doi:10.1111/j.2042-7158.1995.tb05801.x. PMID 7791029. S2CID 25311518.
[6]
Nishio H, Inoue A, Nakata Y (1996). "Binding affinity of sarpogrelate, a new antiplatelet agent, and its metabolite for serotonin receptor subtypes". Archives Internationales de Pharmacodynamie et de Therapie. 331 (2): 189–202. PMID 8937629.
[7]
Rashid M, Manivet P, Nishio H, Pratuangdejkul J, Rajab M, Ishiguro M, et al. (May 2003). "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". Life Sci. 73 (2): 193–207. doi:10.1016/s0024-3205(03)00227-3. PMID 12738034.
[8]
Muntasir HA, Hossain M, Bhuiyan MA, Komiyama T, Nakamura T, Ozaki M, et al. (July 2007). "Identification of a key amino acid of the human 5-HT(2B) serotonin receptor important for sarpogrelate binding". Journal of Pharmacological Sciences. 104 (3): 274–7. doi:10.1254/jphs.sc0060241. PMID 17609583.
[9]
Pietraszek MH, Takada Y, Taminato A, Yoshimi T, Watanabe I, Takada A (April 1993). "The effect of MCI-9042 on serotonin-induced platelet aggregation in type 2 diabetes mellitus". Thrombosis Research. 70 (2): 131–8. doi:10.1016/0049-3848(93)90154-g. PMID 8322284.
[10]
Ogawa S, Takeuchi K, Sugimura K, Sato C, Fukuda M, Lee R, et al. (1999). "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 & Physiology. 26 (5–6): 461–4. doi:10.1111/j.1440-1681.1999.03056.x. PMID 10386239. S2CID 31041268.{{cite journal}}: CS1 maint: overridden setting (link)
[11]
Rydzewski A, Urano T, Hachiya T, Kaneko H, Baba S, Takada Y, et al. (December 1996). "The effect of a 5HT2 receptor antagonist sarpogrelate (MCI-9042) treatment on platelet function in Buerger's disease". Thrombosis Research. 84 (6): 445–52. doi:10.1016/s0049-3848(96)00212-5. PMID 8987165.
[12]
Igarashi M, Okuda T, Oh-i T, Koga M (October 2000). "Changes in plasma serotonin concentration and acceleration plethysmograms in patients with Raynaud's phenomenon after long-term treatment with a 5-HT2 receptor antagonist". The Journal of Dermatology. 27 (10): 643–50. doi:10.1111/j.1346-8138.2000.tb02246.x. PMID 11092268. S2CID 24884976.
[13]
Satomura K, Takase B, Hamabe A, Ashida K, Hosaka H, Ohsuzu F, et al. (January 2002). "Sarpogrelate, a specific 5HT2-receptor antagonist, improves the coronary microcirculation in coronary artery disease". Clinical Cardiology. 25 (1): 28–32. doi:10.1002/clc.4950250108. PMC 6654074. PMID 11808836.
[14]
Kinugawa T, Fujita M, Lee JD, Nakajima H, Hanada H, Miyamoto S (August 2002). "Effectiveness of a novel serotonin blocker, sarpogrelate, for patients with angina pectoris". American Heart Journal. 144 (2): A1–A6. doi:10.1067/mhj.2002.124056. PMID 12177659.
[15]
Hayashi T, Sumi D, Matsui-Hirai H, Fukatsu A, Arockia Rani PJ, Kano H, et al. (May 2003). "Sarpogrelate HCl, a selective 5-HT2A antagonist, retards the progression of atherosclerosis through a novel mechanism". Atherosclerosis. 168 (1): 23–31. doi:10.1016/s0021-9150(03)00054-6. PMID 12732383.{{cite journal}}: CS1 maint: overridden setting (link)
[16]
"Sarpogrelate". PubChem. Retrieved 24 November 2024.
[17]
Saini HK, Takeda N, Goyal RK, Kumamoto H, Arneja AS, Dhalla NS (2004). "Therapeutic potentials of sarpogrelate in cardiovascular disease". Cardiovasc Drug Rev. 22 (1): 27–54. doi:10.1111/j.1527-3466.2004.tb00130.x. PMID 14978517.
[18]
Hashizume H, Kawakami M, Yoshida M, Okada M, Enyo Y, Inomata Y (February 2007). "Sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, attenuates neurogenic pain induced by nucleus pulposus in rats". Spine (Phila Pa 1976). 32 (3): 315–320. doi:10.1097/01.brs.0000253601.35732.c1. PMID 17268262.
[19]
Obata H, Saito S, Ishizaki K, Goto F (September 2000). "Antinociception in rat by sarpogrelate, a selective 5-HT(2A) receptor antagonist, is peripheral". Eur J Pharmacol. 404 (1–2): 95–102. doi:10.1016/s0014-2999(00)00522-7. PMID 10980267.
[20]
Nishiyama T (May 2005). "Effects of a 5-HT2A receptor antagonist, sarpogrelate on thermal or inflammatory pain". Eur J Pharmacol. 516 (1): 18–22. doi:10.1016/j.ejphar.2005.04.026. PMID 15916757. 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.
[21]
Komatsu T, Enjouji S, Nakai H, Inokuchi T, Iida S (1991). "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". Drug Metabolism and Pharmacokinetics. 6 (3): 377–398. doi:10.2133/dmpk.6.377. ISSN 0916-1139.

Sarpogrelate

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References

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