5-HT2B receptor

5-HT2B receptor

5-hydroxytryptamine (serotonin) receptor 2B, G protein-coupled
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols  ; 5-HT(2B); 5-HT2B
External IDs IUPHAR: ChEMBL: GeneCards:
RNA expression pattern
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene.[1][2] 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT).


  • Function 1
  • Clinical significance 2
  • Ligands 3
    • Agonists 3.1
    • Antagonists 3.2
  • Possible applications 4
  • See also 5
  • References 6
  • External links 7
  • Further reading 8


The 5-HT2 receptors (of which the 5-HT2B receptor is a subtype) mediate many of the central and peripheral physiologic functions of serotonin. Cardiovascular effects include contraction of blood vessels and shape changes in platelets; central nervous system effects include neuronal sensitization to tactile stimuli and mediation of some of the effects of hallucinogenic substituted amphetamines.

The 5-HT2B receptor subtype is involved in:

  • CNS: presynaptic inhibition, behavioural effects[3]
  • Vascular: pulmonary vasoconstriction[4]
  • Cardiac: The 5-HT2B receptor regulates cardiac structure and functions as demonstrated by the abnormal cardiac development observed in 5-HT2B receptor null mice.[5] The 5-HT2B receptor stimulation can also lead to pathological proliferation of cardiac valves fibroblasts,[6] which with chronic overstimulation of 5-HT2B can lead to a severe valvulopathy. Moreover, 5-HT2B receptors were recently shown to be overexpressed in human failing heart and antagonists of 5-HT2B receptors were uncovered to prevent both angiotensin II or beta-adrenergic agonist-induced pathological cardiac hypertrophy in mouse.[7][8][9]
  • Serotonin transporter: 5-HT2B receptors regulate serotonin release via the serotonin transporter, and are important both to normal physiological regulation of serotonin levels in blood plasma,[10] and with the abnormal acute serotonin release produced by drugs such as MDMA.[3] Surprisingly however 5-HT2B receptor activation appears to be protective against the development of serotonin syndrome following elevated extracellular serotonin levels,[11] despite its role in modulating serotonin release.

Clinical significance

5-HT2B receptors have also been strongly implicated in drug-induced valvular heart disease.[12][13][14] In this context, it is generally considered to be an antitarget.

The structure of the 5-HT2B receptor was recently solved in complex with the valvulopathogenic drug ergotamine.[15]


As of 2009, few highly selective 5-HT2B receptor ligands have been discovered, although numerous potent non-selective compounds are known, particularly agents with concomitant 5-HT2C binding. Research in this area has been limited due to the cardiotoxicity of 5-HT2B agonists, and the lack of clear therapeutic application for 5-HT2B antagonists, but there is still a need for selective ligands for scientific research.[16]


  • BW-723C86:[17] fair functional subtype selectivity; almost full agonist. Anxiolytic in vivo.[18]
  • Ro60-0175 [17] functionally selective over 5-HT2A, potent agonist at both 5-HT2B/C
  • VER-3323: selective for 5-HT2B/C over 5-HT2A
  • α-Methyl-5-HT - moderately selective over 5-HT2A/C
  • 6-APB


Possible applications

5-HT2B antagonists have previously been proposed as treatment for migraine headaches, and RS-127,445 was trialled in humans up to Phase I for this indication, but development was not continued.[29] More recent research has focused on possible application of 5-HT2B antagonists as treatments for chronic heart disease.[30][31] Serotonin 5-HT2B receptors inhibit liver regeneration [32] and may have effects on immune system function.

See also


  1. ^ 5-hydroxytryptamine (serotonin) receptor 2B"2B"Entrez Gene: HTR. 
  2. ^ Schmuck K, Ullmer C, Engels P, Lübbert H (March 1994). serotonin receptor"2B"Cloning and functional characterization of the human 5-HT. FEBS Lett. 342 (1): 85–90.  
  3. ^ a b Doly S, Valjent E, Setola V, Callebert J, Hervé D, Launay JM, Maroteaux L (March 2008). "Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro". J. Neurosci. 28 (11): 2933–40.  
  4. ^ Launay JM, Hervé P, Peoc'h K, Tournois C, Callebert J, Nebigil CG, Etienne N, Drouet L, Humbert M, Simonneau G, Maroteaux L (October 2002). "Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension". Nat. Med. 8 (10): 1129–35.  
  5. ^ Nebigil CG, Hickel P, Messaddeq N, Vonesch JL, Douchet MP, Monassier L, György K, Matz R, Andriantsitohaina R, Manivet P, Launay JM, Maroteaux L (June 2001). "Ablation of serotonin 5-HT(2B) receptors in mice leads to abnormal cardiac structure and function". Circulation 103 (24): 2973–9.  
  6. ^ Elangbam CS, Job LE, Zadrozny LM, Barton JC, Yoon LW, Gates LD, Slocum N (August 2008). "5-hydroxytryptamine (5HT)-induced valvulopathy: compositional valvular alterations are associated with 5HT2B receptor and 5HT transporter transcript changes in Sprague-Dawley rats". Exp. Toxicol. Pathol. 60 (4–5): 253–62.  
  7. ^ Jaffré F, Callebert J, Sarre A, Etienne N, Nebigil CG, Launay JM, Maroteaux L, Monassier L (August 2004). "Involvement of the serotonin 5-HT2B receptor in cardiac hypertrophy linked to sympathetic stimulation: control of interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha cytokine production by ventricular fibroblasts". Circulation 110 (8): 969–74.  
  8. ^ Monassier L, Laplante MA, Jaffré F, Bousquet P, Maroteaux L, de Champlain J (August 2008). "Serotonin 5-HT(2B) receptor blockade prevents reactive oxygen species-induced cardiac hypertrophy in mice". Hypertension 52 (2): 301–7.  
  9. ^ Jaffré F, Bonnin P, Callebert J, Debbabi H, Setola V, Doly S, Monassier L, Mettauer B, Blaxall BC, Launay JM, Maroteaux L (November 2008). "Serotonin and Angiotensin Receptors in Cardiac Fibroblasts Coregulate Adrenergic-Dependent Cardiac Hypertrophy". Circ. Res. 104 (1): 113–23.  
  10. ^ Callebert J, Esteve JM, Hervé P, Peoc'h K, Tournois C, Drouet L, Launay JM, Maroteaux L (May 2006). "Evidence for a control of plasma serotonin levels by 5-hydroxytryptamine(2B) receptors in mice". J. Pharmacol. Exp. Ther. 317 (2): 724–31.  
  11. ^ Diaz SL, Maroteaux L (January 2011). "Implication of 5-HT(2B) receptors in the serotonin syndrome". Neuropharmacology 61 (3): 495–502.  
  12. ^ Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL (December 2000). "Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications". Circulation 102 (23): 2836–41.  
  13. ^ Fitzgerald LW, Burn TC, Brown BS, Patterson JP, Corjay MH, Valentine PA, Sun JH, Link JR, Abbaszade I, Hollis JM, Largent BL, Hartig PR, Hollis GF, Meunier PC, Robichaud AJ, Robertson DW (January 2000). "Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine". Mol. Pharmacol. 57 (1): 75–81.  
  14. ^ Roth BL (January 2007). "Drugs and valvular heart disease". N. Engl. J. Med. 356 (1): 6–9.  
  15. ^  
  16. ^ Schuhmacher M (2007). -receptor antagonists: synthesis, analysis and in-vitro pharmacology] (German)"2B"[Chiral arylmethoxytryptamines as 5-HT. Ph.D. Dissertation. University of Regensburg. pp. pages 6–17. Retrieved 2008-08-11. 
  17. ^ a b c Porter RH, Benwell KR, Lamb H, et al. (1999). "Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells". Br. J. Pharmacol. 128 (1): 13–20.  
  18. ^ Kennett GA, Trail B, Bright F (December 1998). "Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated". Neuropharmacology 37 (12): 1603–10.  
  19. ^ a b Setola, Vincent; Sandra J Hufeisen; K Jane Grande-Allen; Ivan Vesely; Richard A Glennon; Bruce Blough; Richard B Rothman; Bryan L Roth (Jan 7, 2003). "3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro". Molecular Pharmacology 63 (6): 1223–1229.  
  20. ^ Ray TS; Manzoni, Olivier Jacques (2010). Manzoni, Olivier Jacques, ed. "Psychedelics and the Human Receptorome". PLoS ONE 5 (2): e9019.  
  21. ^ Görnemann T, Hübner H, Gmeiner P, et al. (2008). "Characterization of the molecular fragment that is responsible for agonism of pergolide at serotonin 5-Hydroxytryptamine2B and 5-Hydroxytryptamine2A receptors". J. Pharmacol. Exp. Ther. 324 (3): 1136–45.  
  22. ^ Hofmann C, Penner U, Dorow R, Pertz HH, Jähnichen S, Horowski R, Latté KP, Palla D, Schurad B (2006). "Lisuride, a dopamine receptor agonist with 5-HT2B receptor antagonist properties: absence of cardiac valvulopathy adverse drug reaction reports supports the concept of a crucial role for 5-HT2B receptor agonism in cardiac valvular fibrosis". Clin Neuropharmacol 29 (2): 80–6.  
  23. ^ Egan CT, Herrick-Davis K, Miller K, Glennon RA, Teitler M (April 1998). "Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors". Psychopharmacology (Berl.) 136 (4): 409–14.  
  24. ^ Beattie DT, Smith JA, Marquess D, et al. (November 2004). "The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo". Br. J. Pharmacol. 143 (5): 549–60.  
  25. ^ Bonhaus DW, Flippin LA, Greenhouse RJ, et al. (1999). "RS-127445: a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist". Br. J. Pharmacol. 127 (5): 1075–82.  
  26. ^ Kovács A, Gacsályi I, Wellmann J, et al. (2003). "Effects of EGIS-7625, a selective and competitive 5-HT2B receptor antagonist". Cardiovasc Drugs Ther 17 (5–6): 427–34.  
  27. ^ Dunlop J, Lock T, Jow B, et al. (March 2009). "Old and new pharmacology: positive allosteric modulation of the alpha7 nicotinic acetylcholine receptor by the 5-hydroxytryptamine(2B/C) receptor antagonist SB-206553 (3,5-dihydro-5-methyl-N-3-pyridinylbenzo[1,2-b:4,5-b']di pyrrole-1(2H)-carboxamide)". J. Pharmacol. Exp. Ther. 328 (3): 766–76.  
  28. ^ Reavill C, Kettle A, Holland V, Riley G, Blackburn TP (February 1999). "Attenuation of haloperidol-induced catalepsy by a 5-HT2C receptor antagonist". Br. J. Pharmacol. 126 (3): 572–4.  
  29. ^ Poissonnet G, Parmentier JG, Boutin JA, Goldstein S (March 2004). "The emergence of selective 5-HT 2B antagonists structures, activities and potential therapeutic applications". Mini Rev Med Chem 4 (3): 325–30.  
  30. ^ Shyu KG (January 2009). "Serotonin 5-HT2B receptor in cardiac fibroblast contributes to cardiac hypertrophy: a new therapeutic target for heart failure?". Circulation Research 104 (1): 1–3.  
  31. ^ Moss N, Choi Y, Cogan D, Flegg A, Kahrs A, Loke P, Meyn O, Nagaraja R, Napier S, Parker A, Thomas Peterson J, Ramsden P, Sarko C, Skow D, Tomlinson J, Tye H, Whitaker M (April 2009). "A new class of 5-HT2B antagonists possesses favorable potency, selectivity, and rat pharmacokinetic properties". Bioorganic & Medicinal Chemistry Letters 19 (8): 2206–10.  
  32. ^ Ebrahimkhani MR, Oakley F, Murphy LB, Mann J, Moles A, Perugorria MJ, Ellis E, Lakey AF, Burt AD, Douglass A, Wright MC, White SA, Jaffré F, Maroteaux L, Mann DA (December 2011). "Stimulating healthy tissue regeneration by targeting the 5-HT₂B receptor in chronic liver disease". Nat. Med. 17 (12): 1668–73.  

External links

  • "2B"5-HT. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 

Further reading

  • Raymond JR, Mukhin YV, Gelasco A, et al. (2002). "Multiplicity of mechanisms of serotonin receptor signal transduction". Pharmacol. Ther. 92 (2–3): 179–212.  
  • Bonhaus DW, Bach C, DeSouza A, et al. (1995). "The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors". Br. J. Pharmacol. 115 (4): 622–8.  
  • Choi DS, Birraux G, Launay JM, Maroteaux L (1994). "The human serotonin 5-HT2B receptor: pharmacological link between 5-HT2 and 5-HT1D receptors". FEBS Lett. 352 (3): 393–9.  
  • Kursar JD, Nelson DL, Wainscott DB, Baez M (1994). "Molecular cloning, functional expression, and mRNA tissue distribution of the human 5-hydroxytryptamine2B receptor". Mol. Pharmacol. 46 (2): 227–34.  
  • Schmuck K, Ullmer C, Engels P, Lübbert H (1994). "Cloning and functional characterization of the human 5-HT2B serotonin receptor". FEBS Lett. 342 (1): 85–90.  
  • Launay JM, Birraux G, Bondoux D, et al. (1996). "Ras involvement in signal transduction by the serotonin 5-HT2B receptor". J. Biol. Chem. 271 (6): 3141–7.  
  • Le Coniat M, Choi DS, Maroteaux L, et al. (1996). "The 5-HT2B receptor gene maps to 2q36.3-2q37.1". Genomics 32 (1): 172–3.  
  • Kim SJ, Veenstra-VanderWeele J, Hanna GL, et al. (2000). "Mutation screening of human 5-HT(2B)receptor gene in early-onset obsessive-compulsive disorder". Mol. Cell. Probes 14 (1): 47–52.  
  • Manivet P, Mouillet-Richard S, Callebert J, et al. (2000). "PDZ-dependent activation of nitric-oxide synthases by the serotonin 2B receptor". J. Biol. Chem. 275 (13): 9324–31.  
  • Becamel C, Figge A, Poliak S, et al. (2001). "Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1". J. Biol. Chem. 276 (16): 12974–82.  
  • Manivet P, Schneider B, Smith JC, et al. (2002). "The serotonin binding site of human and murine 5-HT2B receptors: molecular modeling and site-directed mutagenesis". J. Biol. Chem. 277 (19): 17170–8.  
  • Borman RA, Tilford NS, Harmer DW, et al. (2002). "5-HT2B receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro". Br. J. Pharmacol. 135 (5): 1144–51.  
  • Mammalian Gene Collection Program Team; Strausberg, R. L.; Feingold, E. A.; Grouse, L. H. et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences".  
  • Matsuda A, Suzuki Y, Honda G, et al. (2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways". Oncogene 22 (21): 3307–18.  
  • Slominski A, Pisarchik A, Zbytek B, et al. (2003). "Functional activity of serotoninergic and melatoninergic systems expressed in the skin". J. Cell. Physiol. 196 (1): 144–53.  
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7.  
  • Lin Z, Walther D, Yu XY, et al. (2005). "The human serotonin receptor 2B: coding region polymorphisms and association with vulnerability to illegal drug abuse". Pharmacogenetics 14 (12): 805–11.  
  • Hillier LW, Graves TA, Fulton RS, et al. (2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4". Nature 434 (7034): 724–31.  

This article incorporates text from the United States National Library of Medicine, which is in the public domain.