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. doi: 10.1111/j.2042-7158.1995.tb05801.x.


The new antiplatelet agent sarpogrelate (MCI-9042), its major metabolite (R,S)-1-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2- propanol ((R,S)-M-1) and the enantiomers of (R,S)-M-1 were studied as antagonists at 5-HT2A receptors, 5-HT1-like receptors, 5-HT3 receptors, alpha 1-adrenoceptors, beta-adrenoceptors, histamine H1 receptors, histamine H2 receptors and muscarinic M3 receptors in various functional in-vitro assays. Sarpogrelate, (R,S)-M-1, (R)-M-1 and (S)-M-1, respectively, were competitive antagonists of 5-hydroxytryptamine (5-HT) at 5-HT2A receptors of rat tail artery with calculated pA2 values of 8.53, 9.04, 9.00 and 8.81, respectively. Sarpogrelate lacked prominent 5-HT1-like, 5-HT3, beta, H1, H2 and M3 antagonist activity and weakly blocked alpha 1-adrenoceptors (pKB = 6.30). (S)-M-1 showed weak affinity for 5-HT1-like receptors (pKB = 6.30), alpha 1- (pKB = 6.80) and beta- (pKB = 6.54) adrenoceptors, while (R)-M-1 was a weak antagonist at histamine H1 receptors (pKB = 6.49). Stereoselectivity of M-1 enantiomers was low. (R)-M-1 showed 1.6-fold, 2,3-fold and 2.5-fold higher antagonist activity than (S)-M-1 for 5-HT2A, H1 and M3 receptor, respectively. Affinity at beta-adrenoceptors and 5-HT1-like receptors was 5-fold and 3-fold higher for (S)-M-1 than for (R)-M-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Animals
  • Female
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects*
  • Ritanserin / pharmacology*
  • Serotonin Antagonists / pharmacology*
  • Stereoisomerism
  • Succinates / pharmacology*
  • Tail / blood supply
  • Vasoconstriction / drug effects*


  • Receptors, Serotonin
  • Serotonin Antagonists
  • Succinates
  • Ritanserin
  • sarpogrelate