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

@article{Pertz1995InvitroPO,
  title={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},
  author={Heinz H. Pertz and Sigurd Elz},
  journal={Journal of Pharmacy and Pharmacology},
  year={1995},
  volume={47}
}
  • H. Pertz, S. Elz
  • Published 1 April 1995
  • Biology, Chemistry
  • Journal of Pharmacy and Pharmacology
The new antiplatelet agent sarpogrelate (MCI‐9042), its major metabolite (R,S)‐1‐[2‐[2‐(3‐methoxyphe‐nyl)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, α1‐adrenoceptors, β‐adrenoceptors, histamine H1 receptors, histamine H2 receptors and muscarinic M3 receptors in various functional in‐vitro assays. 
New Oxadiazole Derivatives Showing partly Antiplatelet, Antithrombotic and Serotonin Antagonistic Properties
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The antithrombotic effects of some compounds were small but significant (7–10 % inhibition of thrombus formation).
Synthesis and 5‐HT2A Antagonist Activity of Derivatives of the Novel Heterocycles Indolo[3,2‐d]pyrrolo[3,2‐g]azecine and Benzo[d]pyrrolo[3,2‐g]azecine compared to the Benz[d]indolo[2,3‐g]azecine Derivative LE 300
TLDR
Two benzo[d]pyrrolo[3,2‐g]azecine analogue of the potent dopamine receptor antagonist LE 300 competitively inhibited 5‐HT‐induced contractions with similar nanomolar potency but were less active than the reference antagonist ketanserin.
Benzophenone Derivatives and Related Compounds as Potent Histamine H3‐Receptor Antagonists and Potential PET/SPECT Ligands
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A receptor profile of several functional in vitro assays for several biogenic amine receptors for the meta'‐iodinated derivative demonstrated high selectivity toward the histamine H3 receptor.
Synthesis and Pharmacology of Combined Histamine H1‐/H2‐Receptor Antagonists Containing Diphenhydramine and Cyproheptadine Derivatives
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12 compounds were obtained that proved in vitro to possess high H1‐ and H2‐receptor antagonist activity at the isolated guinea‐pig ileum (H1) and the isolated Guinea‐Pig right atrium (H2), respectively.
Novel Fused Pyrrole Heterocyclic Ring Systems as Structure Analogs of LE 300: Synthesis and Pharmacological Evaluation as Serotonin 5‐HT2A, Dopamine and Histamine H1 Receptor Ligands
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Removal of the hydrophobic moiety (phenyl ring) and replacement of the indole moiety with a 1H‐pyrrole counterpart led to a dramatic alteration in the profile of activity of such azecine‐type compounds.
Selective Inhibition of Cytochrome P450 2D6 by Sarpogrelate and Its Active Metabolite, M-1, in Human Liver Microsomes
TLDR
It is suggested that sarpogrelate could have an effect on the metabolic clearance of drugs possessing CYP2D6-catalyzed metabolism as a major clearance pathway, thereby eliciting pharmacokinetic drug–drug interactions.
Effects of sarpogrelate, a novel 5-HT2 antagonist, on 5-HT-induced endothelium-dependent relaxations in porcine coronary artery.
TLDR
Findings suggest that sarpogrelate has the lowest antagonistic effect on 5-HT-induced endothelium-dependent relaxation and the highest selectivity towards 5- HT2A receptor and might also be the safest drug with respect to its clinical implications in comparison with ritanserin and cyproheptadine.
Influence of bulky substituents on histamine h(3) receptor agonist/antagonist properties.
TLDR
Novel derivatives of 3-(1H-imidazol-4-yl)propanol designed on the basis of lead compounds belonging to the carbamate or ether series possessing (partial) agonist properties on screening assays of the histamine H(3) receptor exhibited partial or full agonist activity in the brain at low dosages under in vivo conditions after oral administration to mice.
DMD054296 33..39
  • Biology, Chemistry
  • 2013
TLDR
Sarpogrelate could have an effect on the metabolic clearance of drugs possessing CYP2D6catalyzed metabolism as a major clearance pathway, thereby eliciting pharmacokinetic drug–drug interactions.
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The antiplatelet agent MCI9042 (sarpogrelate) and its metabolites ((R)-M-I and (9-M-I) are allosteric activators of the 5-HT,, receptor system
  • Naunyn Schmiedebergs Arch. Pharmacol
  • 1994
-HT) contracts the guineapig isolated iliac artery via S-HT,-like and 5-HT, receptors
  • Naunyn Schmiedebergs Arch. Pharmacol
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