Effects of EGIS-7625, a Selective and Competitive 5-HT2B Receptor Antagonist

  title={Effects of EGIS-7625, a Selective and Competitive 5-HT2B Receptor Antagonist},
  author={Anik{\'o} Kov{\'a}cs and Istv{\'a}n Gacs{\'a}lyi and Janos Dr. Wellmann and {\'E}va Schmidt and Z Sz{\"u}cs and Val{\'e}rie Dubreuil and Jean Paul Nicolas and Jean A. Boutin and D{\'a}niel B{\'o}zsing and Andr{\'a}s Egyed and K. Tihanyi and Michael Spedding and G{\'a}bor Sz{\'e}n{\'a}si},
  journal={Cardiovascular Drugs and Therapy},
Our aim was to specify the 5-HT2 subtype selectivity of EGIS-7625 (1-benzyl-4-[(2-nitro-4-methyl-5-amino)-phenyl]-piperazine), a new 5-HT2B ligand, in receptor binding studies and characterize its pharmacology at 5-HT2A, 5-HT2B and 5-HT2C receptors in in vivo experiments and in isolated organs, in vitro. EGIS-7625 had high affinity for recombinant human 5-HT2B receptors (pKi = 9.0) but much weaker affinity for 5-HT2A and 5-HT2C receptors (pKi = 6.2 and 7.7, respectively). In the classic 5-HT2B… 

5-Hydroxytryptamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Unique amongst the GPCRs, RNA editing produces 5-HT2C receptor isoforms that differ in function, such as efficiency and specificity of coupling to Gq/11 and also pharmacology [40, 482].

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The present review focuses on the new therapeutic applications of 5-HT(2B) receptor ligands as well as on the potential concerns.

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In the efforts to discover selective 5‐ HT7R antagonists or agonists, aryl biphenyl‐3‐ylmethylpiperazines were designed, synthesized, and biologically evaluated against the 5‐HT7R to find a best binder and the selectivity profile of compound 28 over other serotonin receptor subtypes.

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This review provides a succinct overview of recent developments in generating and analyzing high-resolution structures of serotonin receptors obtained using crystallography and cryo-electron microscopy and envision that a judicious combination of analysis of high- resolution structures and receptor-lipid interaction would allow a comprehensive understanding of GPCR structure, function and dynamics, thereby leading to efficient drug discovery.

Fingerprint-Based Machine Learning Approach to Identify Potent and Selective 5-HT2BR Ligands

The combined methodology of ligand-based and structure-based methods was validated prospectively, resulting in the identification of hits with nanomolar affinity and ten-fold to ten thousand-fold selectivities.

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The results suggest that 5-HT2C receptor agonism is associated with therapeutic potential in obsessive compulsive disorder and depression.

Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences.

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Novel discriminatory ligands for 5-HT2B receptors

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  • Biology, Chemistry
    Behavioural Brain Research
  • 1995

Characterization of 5-hydroxytryptamine receptors in rat stomach fundus.

1-Arylpiperazines caused a serotonin (5-HT) receptor-mediated contraction of rat fundic strips, which resembles the 5-HT1 recognition site in rat brain cortex, but identity remains unproven.

Mediation by 5‐hydroxytryptamine2B receptors of endothelium‐dependent relaxation in rat jugular vein

The nature of the 5‐HT2 receptor subtype present in this preparation is defined and data are consistent with the presence of 5‐ HT2B receptors mediating endothelium‐dependent relaxation of rat jugular vein.

Further characterization of 5‐hydroxytryptamine receptors (putative 5‐HT2B) in rat stomach fundus longitudinal muscle

It is concluded that despite small differences concerning the enantiomeric selectivity and affinity of rauwolscine and yohimbine, the close pharmacological identity of 5‐HT receptors in rat stomach fundus and the recently cloned 5‐ HT2B receptor is maintained.

5-HT2B-receptor antagonist LY-272015 is antihypertensive in DOCA-salt-hypertensive rats.

The novel hypothesis that 5-HT2B-receptor expression is induced during the development of DOCA-salt hypertension and contributes to the maintenance of severe blood pressure elevations is supported.