ArticleBritish journal of pharmacology1999
RS-127445: a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist.
Article in British journal of pharmacology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 117 citations in OpenAlex.
- Perioperative Esmolol Is Associated with Early Opioid Sparing in Patients with Ischemic Heart Disease: Evidence from a Retrospective Cohort and an Incisional Pain Rat Model.Current medical science · 2026Article
- Ergotamine enhances circadian amplitude and diurnally mitigates nitroglycerin-induced mechanical hypersensitivity.The journal of headache and pain · 2025Article
- Potent and Selective Human 5-HTJournal of medicinal chemistry · 2024Article
- Structure activity relationships of 5-HTEuropean journal of medicinal chemistry · 2023Article
- Synergistic Interaction of 5-HTInternational journal of molecular sciences · 2023Article
- 2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery.Journal of medicinal chemistry · 2023Review
- "Selective" serotonin 5-HTBiochemical pharmacology · 2022Review
- Targeting 5-HTCirculation · 2021Article
- Structure, Function, and Pharmaceutical Ligands of 5-Hydroxytryptamine 2B Receptor.Pharmaceuticals (Basel, Switzerland) · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Pharmacophore-based tailoring of biphenyl amide derivatives as selective 5-hydroxytryptamine 2B receptor antagonists.MedChemComm · 2018Article
- Fingerprint-Based Machine Learning Approach to Identify Potent and Selective 5-HTMolecules (Basel, Switzerland) · 2018Article
- αFrontiers in pharmacology · 2018Article
- Serotonin 2B Receptors in Mesoaccumbens Dopamine Pathway Regulate Cocaine Responses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- A systematic investigation of the differential roles for ventral tegmentum serotonin 1- and 2-type receptors on food intake in the rat.Brain research · 2016Article
- A human and animal model-based approach to investigating the anti-inflammatory profile and potential of the 5-HT2B receptor antagonist AM1030.Journal of inflammation (London, England) · 2016Article
- Trazodone regulates neurotrophic/growth factors, mitogen-activated protein kinases and lactate release in human primary astrocytes.Journal of neuroinflammation · 2015Article
- C4 phenyl aporphines with selective h5-HT(2B) receptor affinity.Bioorganic & medicinal chemistry letters · 2015Article
- The Concise Guide to PHARMACOLOGY 2013/14: G protein-coupled receptors.British journal of pharmacology · 2013Article
- Motoneuron excitability and muscle spasms are regulated by 5-HT2B and 5-HT2C receptor activity.Journal of neurophysiology · 2011Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Efforts to define precisely the role of 5-HT2B receptors in normal and disease processes have been hindered by the absence of selective antagonists. To address this deficiency, we developed a series of naphthylpyrimidines as potentially useful 5-HT2B receptor antagonists. RS-127445 (2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine) was found to have nanomolar affinity for the 5-HT2B receptor (pKi = 9.5+/-0.1) and 1,000 fold selectivity for this receptor as compared to numerous other receptor and ion channel binding sites. In cells expressing human recombinant 5-HT2B receptors, RS-127445 potently antagonized 5-HT-evoked formation of inositol phosphates (pK(B) = 9.5+/-0.1) and 5-HT-evoked increases in intracellular calcium (pIC50 = 10.4+/-0.1). RS-127445 also blocked 5-HT-evoked contraction of rat isolated stomach fundus (pA2 = 9.5+/-1.1) and (+/-)alpha-methyl-5-HT-mediated relaxation of the rat jugular vein (pA2 = 9.9+/-0.3). RS-127445 had no detectable intrinsic activity in these assays. In rats, the fraction of RS-127445 that was bioavailable via the oral or intraperitoneal routes was 14 and 60% respectively. Intraperitoneal administration of RS-127445 (5 mg kg(-1)) produced plasma concentrations predicted to fully saturate accessible 5-HT2B receptors for at least 4 h. In conclusion, RS-127445 is a selective, high affinity 5-HT2B receptor antagonist suitable for use is vivo. The therapeutic potential of this molecule is being further evaluated.
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