Sarpogrelate Explained

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. 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.[17]

See also

Notes and References

  1. 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 . The Journal of Pharmacy and Pharmacology . 47 . 4 . 310–6 . April 1995 . 7791029 . 10.1111/j.2042-7158.1995.tb05801.x . 25311518 .
  2. 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 . 331 . 2 . 189–202 . 8937629 .
  3. Rashid M, Manivet P, Nishio H, Pratuangdejkul J, Rajab M, Ishiguro M, Launay JM, Nagatomo T . 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 . May 2003 . 12738034 . 10.1016/s0024-3205(03)00227-3 .
  4. 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 . 104 . 3 . 274–7 . July 2007 . 17609583 . 10.1254/jphs.sc0060241 . free .
  5. 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 . 70 . 2 . 131–8 . April 1993 . 8322284 . 10.1016/0049-3848(93)90154-g .
  6. Ogawa S, Takeuchi K, Sugimura K, Sato C, Fukuda M, Lee R, Ito S, Sato T . 6 . 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 . 1999 . 26 . 5–6 . 461–4 . 10.1111/j.1440-1681.1999.03056.x . 10386239 . 31041268 .
  7. 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 . 84 . 6 . 445–52 . December 1996 . 8987165 . 10.1016/s0049-3848(96)00212-5 .
  8. 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 . The Journal of Dermatology . 27 . 10 . 643–50 . October 2000 . 11092268 . 10.1111/j.1346-8138.2000.tb02246.x . 24884976 .
  9. 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 . 25 . 1 . 28–32 . January 2002 . 11808836 . 10.1002/clc.4950250108 . 6654074 .
  10. 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 . 144 . 2 . A1–A6 . August 2002 . 12177659 . 10.1067/mhj.2002.124056 .
  11. Hayashi T, Sumi D, Matsui-Hirai H, Fukatsu A, Arockia Rani PJ, Kano H, Tsunekawa T, Iguchi A . 6 . Sarpogrelate HCl, a selective 5-HT2A antagonist, retards the progression of atherosclerosis through a novel mechanism . Atherosclerosis . 168 . 1 . 23–31 . May 2003 . 12732383 . 10.1016/s0021-9150(03)00054-6 .
  12. Web site: Sarpogrelate . PubChem . 24 November 2024.
  13. Saini HK, Takeda N, Goyal RK, Kumamoto H, Arneja AS, Dhalla NS . Therapeutic potentials of sarpogrelate in cardiovascular disease . Cardiovasc Drug Rev . 22 . 1 . 27–54 . 2004 . 14978517 . 10.1111/j.1527-3466.2004.tb00130.x .
  14. Hashizume H, Kawakami M, Yoshida M, Okada M, Enyo Y, Inomata Y . Sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, attenuates neurogenic pain induced by nucleus pulposus in rats . Spine (Phila Pa 1976) . 32 . 3 . 315–320 . February 2007 . 17268262 . 10.1097/01.brs.0000253601.35732.c1 .
  15. Obata H, Saito S, Ishizaki K, Goto F . Antinociception in rat by sarpogrelate, a selective 5-HT(2A) receptor antagonist, is peripheral . Eur J Pharmacol . 404 . 1-2 . 95–102 . September 2000 . 10980267 . 10.1016/s0014-2999(00)00522-7 .
  16. Nishiyama T . Effects of a 5-HT2A receptor antagonist, sarpogrelate on thermal or inflammatory pain . Eur J Pharmacol . 516 . 1 . 18–22 . May 2005 . 15916757 . 10.1016/j.ejphar.2005.04.026 . 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 . Teiko . Enjouji . Setsuko . Nakai . Hiroshi . Inokuchi . Tomio . Iida . Seiu . 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 . 1991 . 0916-1139 . 10.2133/dmpk.6.377 . free . 377–398.

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