Background:

Ki: 8.39 nM

Sarpogrelate (MCI-9042) was shown to have the same affinity as ritanserin for 5-HT2A receptors, [1].

The blockade of 5-HT2A receptors can inhibit thrombus formation suppresses platelet aggregation and inhibits vascular smooth muscle cell proliferation [2].

In vitro: The major metabolite (R,S)-M-1, and M-1 enantiomers of sarpogrelate specifically blocked 5-HT at 5-HT2A receptors. The stereochemical configuration of the ligands does not obviously play a key role at binding to the 5-HT2A receptor [2].

In vivo: PAD patients were divided into two groups. One group treated with 100 mg sarpogrelate in oral 3 times one day for 12 weeks (n = 10), while the other group who remained on conventional therapy as control group (n = 11). Forearm blood flow (FBF) and leg blood flow (LBF) responses to reactive hyperemia (RH) and sublingual administration of nitroglycerin (NTG) were measured by strain-gauge plethysmography. After twelve weeks of its administration, FBF and LBF responses during RH exhibited significant increases from 13.2 6 1.7 to 18.1 6 2.2 mL/min every 100 mL tissue (P , 0.01) and from 8.2 6 0.9 to 14.2 6 2.1 mL/min every 100 mL tissue (P , 0.05), respectively. Augmentation of FBF and LBF induced by sarpogrelate responses to RH was maintained at 24 weeks. The control group had no change observed in at each follow-up time point. The changes in FBF and LBF after sublingual NTG were similar during follow-up periods in the two groups. These findings suggest that longterm oral administration of sarpogrelate improves vascular function in patients with PAD [3].

Clinical trial: Clinical study has been conducted.

参考文献:
[1] Nishio H1, Inoue A, Nakata Y.  Binding affinity of sarpogrelate, a new antiplatelet agent, and its metabolite for serotonin receptor subtypes. Arch Int Pharmacodyn Ther. 1996 Mar-Apr;331(2):189-202.
[2] Pertz H1, 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. J Pharm Pharmacol. 1995 Apr;47(4):310-6.
[3] Miyazaki M1, Higashi Y, Goto C, Chayama K, Yoshizumi M, Sanada H, Orihashi K, Sueda T.  Sarpogrelate hydrochloride, a selective 5-HT2A antagonist, improves vascular function in patients with peripheral arterial disease. J Cardiovasc Pharmacol. 2007 Apr;49(4):221-7._x000C_