RS-102221: A Novel High Affinity and Selective, 5-HT2C Receptor Antagonist

  title={RS-102221: A Novel High Affinity and Selective, 5-HT2C Receptor Antagonist},
  author={Douglas W Bonhaus and Klaus Kurt Weinhardt and Mark Taylor and Andre Desouza and P. M. McNeeley and Krystine Szczepanski and David J. Fontana and J. Trinh and Cynthia Rocha and M. W. Dawson and Lee A. Flippin and R. M. Eglen},

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

EGIS-7625 is a potent, selective and competitive 5-HT2B antagonist that seems to be a good research tool for the separation of the functional roles of vascular 5-ht2A and 5- HT2B receptors.

In-vivo assessment of 5-HT and 5-HT antagonistic 2A 2C properties of newer antipsychotics

The effects of serotonin 5-HT receptor ligands on the MK 212 6-chloro-2 1-piperazinyl pyrazine discriminative stimulus and quipazine-induced head twitches were studied in rats, suggesting that the MK212 discriminATIVE stimulus is mediated by 5- HT receptors, while quipazines-in2C duced head twitching are mediated primarily by5-HT receptors.

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].

3-Substituted 1-methyl-3-benzazepin-2-ones as 5-HT2C receptor agonists

The study established the selective 5-HT2C receptor agonist response of compounds 7, 12–14, 24, 30, and 38 which could act as potential lead molecules for the treatment of pathological conditions associated with 5- HT2C receptors.

Pharmacological characterization of an adenylyl cyclase-coupled 5-HT receptor in aplysia: comparison with mammalian 5-HT receptors.

Methiothepin substantially inhibited two effects of 5-HT on SN firing properties that are mediated by a cAMP-dependent reduction in S-K(+) current: spike broadening in tetraethylammonium/nifedipine and increased excitability and cyproheptadine blocked the5-HT-induced increase in SN excitability.

5-HT-2C Receptor

Insights into binding modes of 5-HT2c receptor antagonists with ligand-based and receptor-based methods

A predictive CoMFA model was developed based on the 24 compounds that were used as the training set in the pharmacophore modeling and provided suggestions in the discovery of novel 5-HT2c receptor antagonists.

The Multiplicity of Serotonin Receptors: Uselessly Diverse Molecules or an Embarrassment of Riches?

Evidence that is summarized in this review suggests that 5-HT receptors represent novel therapeutic targets for a number of neurologic and psychiatric diseases including migraine headaches, chronic pain conditions, schizophrenia, anxiety, depression, eating disorders, obsessive compulsive disorder, pervasive developmental disorders, and obesity-related conditions.



Novel discriminatory ligands for 5-HT2B receptors

  • G. Baxter
  • Biology, Chemistry
    Behavioural Brain Research
  • 1995

Potent, selective tetrahydro-beta-carboline antagonists of the serotonin 2B (5HT2B) contractile receptor in the rat stomach fundus.

As the first compounds reported with such selectivity and enhanced receptor affinity, these tetrahydro-beta-carboline antagonists are useful tools for elucidating the role of serotonin acting at the 5HT2B receptor in normal and disease physiology.

Molecular biology of serotonin (5-HT) receptors

m-chlorophenylpiperazine and m-trifluoromethylphenylpiperazine are partial agonists at cloned 5-HT2A receptors expressed in fibroblasts.

Serotonin2A (5-HT2A) and 5-HT2C receptors share numerous pharmacological properties. Two compounds thought to discriminate between these two receptor subtypes are m-chlorophenypiperazine (mCPP) and

5-HT2 receptor subtypes: a family re-united?

In vitro and in vivo profile of SB 206553, a potent 5‐HT2C/5‐HT2B receptor antagonist with anxiolytic‐like properties

The results suggest that SB 206553 is a potent mixed 5‐HT2C/5-HT2B receptor antagonist with selectivity over the 5‐ HT2A and all other sites studied and possesses anxiolytic‐like properties.

5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole: a novel 5-HT2C/5-HT2B receptor antagonist with improved affinity, selectivity, and oral activity.

Of a series of conformationally restricted analogues of indolylurea 1, the 1,2, 3,5-tetrahydropyrrolo[2,3-f]indole derivative, compound 11, was found to be of significant utility as a pharmacological tool to delineate the functional significance of blockade of 5-HT2B and 5- HT2C receptors.

Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes.

In vivo properties of SB 200646A, a 5‐HT2C/2B receptor antagonist

The results indicate that SB 200646A has in vivo efficacy and that 5‐HT2C or 5‐ HT2B receptors are indeed likely to mediate mCPP‐induced hypolocomotion, hypophagia and anxiogenesis and suggest that5‐HT 2C/2B receptor blockade induces anxiolysis.