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Sarpogrelate

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Sarpogrelate
Clinical data
Other namesMCI-9042; LS-187,118
AHFS/Drugs.comInternational Drug Names
ATC code
  • None
Identifiers
  • 4-[2-(dimethylamino)-1-({2-[2-(3-methoxyphenyl)ethyl]phenoxy}methyl)ethoxy]-4-oxobutanoic acid
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC24H31NO6
Molar mass429.513 g·mol−1
3D model (JSmol)
  • CN(C)CC(COC1=CC=CC=C1CCC2=CC(=CC=C2)OC)OC(=O)CCC(=O)O
  • 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)

Sarpogrelate (former developmental code names MCI-9042, LS-187,118) is a drug which acts as an antagonist at the serotonin 5-HT2A[1][2] 5-HT2B, and 5-HT2C receptors.[3][4] However, its affinities for the human 5-HT2C and 5-HT2B receptors are about one and two orders of magnitude lower than for the human 5-HT2A receptor, respectively.[3] The drug blocks serotonin-induced platelet aggregation, and has potential applications in the treatment of many diseases including diabetes mellitus,[5][6] Buerger's disease,[7] Raynaud's disease,[8] coronary artery disease,[9] angina pectoris,[10] and atherosclerosis.[11]

The predicted log P (XLogP3) of sarpogrelate is 1.2.[12] A 2004 review stated that it was unknown whether sarpogrelate crosses the blood–brain barrier.[13] However, other papers have stated that sarpogrelate minimally crosses into the brain and hence is peripherally selective.[14][15][16] Accordingly, a rat study found that peak sarpogrelate levels were 50-fold lower in the brain and spinal cord than in the circulation.[16][17]

See also

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References

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  1. ^ 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.
  2. ^ 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.
  3. ^ a b 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.
  4. ^ 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.
  5. ^ 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.
  6. ^ 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)
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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)
  12. ^ "Sarpogrelate". PubChem. Retrieved 24 November 2024.
  13. ^ 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.
  14. ^ 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.
  15. ^ 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.
  16. ^ a b 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.
  17. ^ 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.
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