Sarpogrelate-d3 (hydrochloride) (Synonyms: MCI-9042-d3)

Sarpogrelate-d₃ is intended for use as an internal standard for the quantification of sarpogrelate (hydrochloride) by GC- or LC-MS. Sarpogrelate is a selective antagonist of the serotonin (5-HT) receptor subtypes 5-HT_2A, 5-HT_2B, and 5-HT_2C (K_is = 3.02, 269, and 37.2 nM, respectively, for human recombinant receptors expressed in CHO-K1 cells).¹ It is selective for 5-HT₂ (K_i = 70.8 nM) over 5-HT₁ (K_i = >26,000 nM), α₁-, α₂-, and β-adrenergic (K_is = 640-123,800 nM), and muscarinic receptors (K_i = >40,000 nM).² In vitro, it inhibits aggregation of rat whole blood induced by collagen, 5-HT with collagen, and 5-HT with ADP .³ In vivo, it inhibits leukocyte-endothelial interactions in the femoral artery induced by a high-fat high-fructose diet (HFFD) in mice when administered at a dose of 5 mg/kg per day.⁴ Sarpogrelate (5 mg/kg per day) decreases ventricular hypertrophy and infarct size in a rat model of myocardial infarction.⁵

1.Rashid, M., Manivet, P., Nishio, H., et al.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 modelingLife Sci.73(2)193-207(2003) 2.Maruyama, K., Kinami, J., Sugita, Y., et al.MCI-9042: High affinity for serotonergic receptors as assessed by radioligand binding assayJ. Pharmacobiodyn.14(4)177-181(1991) 3.Kubacka, M., Kazek, G., Kotańska, M., et al.Anti-aggregation effect of aroxyalkyl derivatives of 2-methoxyphenylpiperazine is due to their 5-HT2A and α2-adrenoceptor antagonistic properties. A comparison with ketanserin, sarpogrelate, prazosin, yohimbine and ARC239Eur. J. Pharmacol.818263-270(2018) 4.Kataoka, H., Ariyama, Y., Deushi, M., et al.Inhibitory effect of serotonin antagonist on leukocyte-endothelial interactions in vivo and in vitroPLoS One11(1)e0147929(2016) 5.Brasil, D., Temsah, R.M., Kumar, K., et al.Blockade of 5-HT2A receptors by sarpogrelate protects the heart against myocardial infarction in ratsJ. Cardiovasc. Pharmacol. Ther.7(1)53-59(2002)