5-HT2B receptor

HTR2B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4NC3, 4IB4
Identifiers
Aliases	HTR2B , 5-HT(2B), 5-HT2B, 5-HT-2B, 5-hydroxytryptamine receptor 2B
External IDs	OMIM: 601122; MGI: 109323; HomoloGene: 55492; GeneCards: HTR2B; OMA:HTR2B - orthologs
Gene location (Human) Chr. Chromosome 2 (human) [1] Band 2q37.1 Start 231,108,230 bp [1] End 231,125,042 bp [1]
Gene location (Mouse) Chr. Chromosome 1 (mouse) [2] Band 1|1 C5 Start 86,026,748 bp [2] End 86,039,692 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in decidua tail of epididymis stromal cell of endometrium caput epididymis corpus epididymis left adrenal gland left adrenal cortex right adrenal cortex smooth muscle tissue testicle Top expressed in decidua morula neural groove neural fold embryo tail of embryo genital tubercle calvaria right lung lobe right kidney More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity GTPase activator activity signal transducer activity G protein-coupled serotonin receptor activity G-protein alpha-subunit binding serotonin binding neurotransmitter receptor activity Cellular component cytoplasm integral component of membrane membrane plasma membrane synapse cell junction neuron projection integral component of plasma membrane nucleoplasm dendrite Biological process intestine smooth muscle contraction smooth muscle contraction G protein-coupled receptor internalization release of sequestered calcium ion into cytosol regulation of behavior positive regulation of endothelial cell proliferation positive regulation of MAP kinase activity phosphorylation positive regulation of cytokine production vasoconstriction ERK1 and ERK2 cascade positive regulation of phosphatidylinositol biosynthetic process cardiac muscle hypertrophy heart morphogenesis cellular calcium ion homeostasis neural crest cell differentiation negative regulation of apoptotic process negative regulation of cell death activation of phospholipase C activity protein kinase C signaling cGMP biosynthetic process cellular response to temperature stimulus positive regulation of GTPase activity heart development positive regulation of nitric-oxide synthase activity protein kinase C-activating G protein-coupled receptor signaling pathway embryonic morphogenesis serotonin receptor signaling pathway neural crest cell migration positive regulation of cell population proliferation positive regulation of ERK1 and ERK2 cascade positive regulation of I-kappaB kinase/NF-kappaB signaling phosphatidylinositol 3-kinase signaling negative regulation of autophagy positive regulation of cell division calcium-mediated signaling signal transduction phospholipase C-activating G protein-coupled receptor signaling pathway G protein-coupled serotonin receptor signaling pathway G protein-coupled receptor signaling pathway animal behavior cGMP-mediated signaling G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger chemical synaptic transmission Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3357 15559 Ensembl ENSG00000135914 ENSMUSG00000026228 UniProt P41595 Q02152 RefSeq (mRNA) NM_000867 NM_001320758 NM_008311 RefSeq (protein) NP_000858 NP_001307687 NP_032337 Location (UCSC) Chr 2: 231.11 – 231.13 Mb Chr 1: 86.03 – 86.04 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

5-Hydroxytryptamine receptor 2B (5-HT_2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene. ^{[5] [6]} 5-HT_2B is a member of the 5-HT₂ receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT₂ receptors, the 5-HT_2B receptor is G_q/G₁₁-protein coupled, leading to downstream activation of phospholipase C.

Tissue distribution and function

First discovered in the stomach of rats, 5-HT_2B was challenging to characterize initially because of its structural similarity to the other 5-HT₂ receptors, particularly 5-HT_2C. ^[7] The 5-HT₂ receptors (of which the 5-HT_2B 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 (CNS) effects include neuronal sensitization to tactile stimuli and mediation of some of the effects of hallucinogenic substituted amphetamines. The 5-HT_2B receptor is expressed in several areas of the CNS, including the dorsal hypothalamus, frontal cortex, medial amygdala, and meninges. ^[8] However, its most important role is in the peripheral nervous system (PNS) where it maintains the viability and efficiency of the cardiac valve leaflets. ^[9]

The 5-HT_2B receptor subtype is involved in:

• CNS: inhibition of serotonin and dopamine uptake, behavioral effects ^[10]
• Vascular: pulmonary vasoconstriction ^[11]
• Cardiac: The 5-HT_2B receptor regulates cardiac structure and functions, as demonstrated by the abnormal cardiac development observed in 5-HT_2B receptor null mice. ^[12] Excessive stimulation of this receptor causes pathological proliferation of cardiac valve fibroblasts, ^[13] with chronic overstimulation leading to valvulopathy. ^{[14] [15]} These receptors are also overexpressed in human failing heart and antagonists of 5-HT_2B receptors were discovered to prevent both angiotensin II or beta-adrenergic agonist-induced pathological cardiac hypertrophy in mouse. ^{[16] [17] [18]}
• Serotonin transporter: 5-HT_2B receptors regulate serotonin release via the serotonin transporter, and are important both to normal physiological regulation of serotonin levels in blood plasma, ^[19] and with the abnormal acute serotonin release produced by drugs such as MDMA. ^[10] Surprisingly, however, 5-HT_2B receptor activation appears to be protective against the development of serotonin syndrome following elevated extracellular serotonin levels, ^[20] despite its role in modulating serotonin release.

Clinical significance

5-HT_2B receptors have been strongly implicated in causing drug-induced valvular heart disease. ^{[21] [22] [23]} The Fen-Phen scandal in the 80s and 90s revealed the cardiotoxic effects of 5-HT_2B stimulation. ^[24] Today, 5-HT_2B agonism is considered a toxicity signal precluding further clinical development of a compound. ^[25]

Ligands

The structure of the 5-HT_2B receptor was resolved in a complex with the valvulopathogenic drug ergotamine. ^[26] As of 2009, few highly selective 5-HT_2B receptor ligands have been discovered, although numerous potent non-selective compounds are known, particularly agents with concomitant 5-HT_2C binding. Research in this area has been limited due to the cardiotoxicity of 5-HT_2B agonists, and the lack of clear therapeutic application for 5-HT_2B antagonists, but there is still a need for selective ligands for scientific research. ^[27]

Agonists

Endogenous

• 5-Methoxytryptamine (5-MT) – trace amine ^{[28] [29]}
• DMT – trace amine ^{[30] [31] [32] [33]}
• Serotonin – neurotransmitter, K_D ≈ 10 nM ^{[34] [35] [36]}
• Tryptamine – trace amine ^{[34] [36]}

Selective

• 6-APB – ~100-fold selectivity over the 5-HT_2A and 5-HT_2C receptors, ≥32-fold selectivity over monoamine release, ~12-fold selectivity over α_2C-adrenergic receptor ^{[30] [37]}
• α-Methylserotonin – ~10-fold selectivity over 5-HT_2A and 5-HT_2C ^{[34] [38] [36]}
• BW-723C86 – 100-fold selectivity over 5-HT_2A but only 3- to 10-fold selectivity over 5-HT_2C, ^{[34] [39]} fair functional subtype selectivity, almost full agonist, anxiolytic in vivo ^[40]
• LY-266,097 – biased partial agonist in favor of G_q protein, no β-arrestin2 recruitment ^[41]
• VU6067416 – modest selectivity over 5-HT_2A and 5-HT_2C ^[42]

Non-selective

• 25C-NBOMe ^{[30] [43]}
• 25I-NBOMe ^{[30] [43]}
• 2C-B ^{[30] [43]}
• 2C-B-FLY ^{[30] [44]}
• 2C-C ^{[30] [43]}
• 2C-D ^{[30] [43]}
• 2C-E ^{[30] [43]}
• 2C-I ^{[30] [43]}
• 4-Methylamphetamine ^[30]
• 5-APB ^{[30] [45] [37]}
• 5-APDB ^[30]
• 5-Carboxamidotryptamine ^[36]
• 5-MAPB ^[45]
• 6-APB ^[37]
• 6-APDB ^[30]
• 6-MAPB ^[45]
• 5-MeO-αMT ^{[30] [32]}
• 5-MeO-DiPT
• 5-MeO-DMT ^[42]
• 5-MeO-MiPT ^{[30] [32]}
• AL-38022A ^[46]
• Aminorex (weakly) ^{[47] [48]}
• Ariadne ^[49]
• Benfluorex ^[50]
• Bromo-dragonfly ^{[44] [51] [52]}
• Bromocriptine ^[53]
• Cabergoline ^{[54] [35]}
• Chlorphentermine (very weakly) ^[47]
• CYB210010 (2C-T-TFM) ^{[55] [56]}
• Dexfenfluramine ^[57]
• Dexnorfenfluramine ^[57]
• Dihydroergocryptine ^[58]
• Dihydroergotamine ^{[54] [59]}
• DiPT ^{[30] [32]}
• DOB ^{[30] [36]}
• DOC ^[30]
• DOET ^[60]
• DOI ^{[30] [36] [35]}
• DOM ^{[30] [60]}
• Ergometrine (ergonovine) ^[54]
• Ergotamine ^{[54] [57] [35]}
• Fenfluramine ^{[57] [35]}
• Fenoldopam ^[35]
• Guanfacine – an α_2A-adrenergic agonist, but has 5-HT_2B agonistic activity at therapeutic concentrations ^{[35] [61]}
• Levofenfluramine ^[57]
• Levonorfenfluramine ^[57]
• Lorcaserin ^[54]
• LSD – about equal affinity for human cloned 5-HT_2B and 5-HT_2A receptors ^{[62] [32] [63]}
• LSM-775 ^[64]
• mCPP (in humans; weak partial agonist) ^{[57] [36]}
• MDA ^{[30] [65]}
• MDMA ^{[33] [65]}
• MEM ^[66]
• Mescaline ^[33]
• Methylergometrine (methylergonovine) ^{[54] [57] [35]}
• Methysergide (antagonist in some studies) ^{[57] [35] [67]}
• Naphthylaminopropane ^[68]
• Norfenfluramine ^{[57] [35] [39]}
• ORG-12962 ^[36]
• ORG-37684 ^[67]
• Oxymetazoline ^[35]
• Pergolide ^{[54] [35] [69]}
• PNU-22394
• Psilocin ^{[62] [63]}
• Psilocybin ^[63]
• Quipazine (weak partial agonist) ^[36]
• Ro60-0175 – functionally selective over 5-HT_2A, potent agonist at both 5-HT_2B/C ^{[34] [39]}
• Ropinirole ^[35]
• Quinidine ^[35]
• TFMPP (weak partial agonist) ^[36]
• VER-3323 – mixed 5-HT_2C and 5-HT_2B agonist with weaker 5-HT_2A affinity ^[67]
• Xylometazoline ^[35]

Peripherally selective

• AL-34662 – non-selective over 5-HT_2A and 5-HT_2C ^[70]

Inactive

A number of notable drugs appear to be inactive or very weak as serotonin 5-HT_2B receptor agonists, at least in vitro . ^[30] These include the stimulants and/or entactogens dextroamphetamine, dextromethamphetamine, 4-fluoroamphetamine, 4-fluoromethamphetamine, phentermine, methylone, mephedrone, MDAI, and MMAI, among others. ^{[30] [47] [37] [71] [72] [73]} Findings are somewhat conflicting for certain psychedelics, such as psilocin and LSD, but most studies find that these drugs are indeed potent serotonin 5-HT_2B receptor agonists. ^{[63] [30] [32]}

Antagonists

Selective

• 5-HCPC ^{[74] [75]}
• 5-HPEC (weak) ^[74]
• 5-HPPC ^[74]
• AM1125 ^[74]
• AM1476 ^[74]
• BF-1 – derived from pimethixene ^{[74] [76] [77]}
• EGIS-7625 – high selectivity over 5-HT_2A ^{[76] [78] [79]}
• EXT5 – highly selective ^{[74] [80]}
• EXT9 – somewhat selective ^{[74] [80]}
• LY-23,728 ^[81]
• LY-266,097 – pK_i = 9.7, 100-fold selectivity over 5-HT_2A and 5-HT_2C ^{[34] [81]}
• LY-272,015 – fairly selective and highly potent ^[34]
• LY-287,375 ^{[81] [82]}
• MRS7925 – substantially selective over 5-HT_2A and 5-HT_2C but minimal selectivity over the adenosine A₁ receptor ^[83]
• MRS8209 ^[84]
• MW071 (MW01-8-071HAB) – non-MAOI minaprine analogue ^[85]
• PRX-08066 – K_i ≈ 1.7 nM, >100-fold selectivity ^{[74] [76] [34]}
• RQ-00310941 (RQ-941) – K_i = 2.0 nM, IC₅₀ = 17 nM, >2,000-fold selectivity against >60 targets, under development for medical use ^{[74] [86] [87]}
• RS-127,445 (MT-500) – K_i = 0.3 nM, >1,000-fold selectivity over 5-HT_2A and 5-HT_2C and numerous other targets, selective over at least eight other serotonin receptors, developed for clinical use but discontinued ^{[74] [34] [76] [88] [67]}
• SB-204,741 – >135-fold selectivity over 5-HT_2C and 5-HT_2A ^[89]
• SB-215,505 – mixed 5-HT_2B and 5-HT_2C antagonist ^{[34] [76] [90]}
• VU6047534 – weak partial agonist or antagonist, peripherally selective in mice but not humans ^{[91] [92]}

Non-selective

• 2-Bromo-LSD (BOL-148; bromolysergide) ^[93]
• (–)-MBP – 5-HT_2A antagonist, 5-HT_2B inverse agonist, and 5-HT_2C agonist ^[94]
• AAZ-A-154 (DLX-001) ^[95]
• Agomelatine – primarily a melatonin MT₁/MT₂ receptor agonist, with a less potent antagonism of 5-HT_2B and 5-HT_2C ^[96]
• AMAP102 (AMAP-102) – 5-HT_2B and 5-HT_2C antagonist ^{[74] [97]}
• Amesergide (LY-237733)
• Amisulpride
• Amitriptyline
• Apomorphine
• Aripiprazole ^[34]
• Asenapine ^[34]
• BMB-201 – and active form BMB-39a ^[98]
• Brexpiprazole
• Brilaroxazine
• C-122 ^{[74] [34]}
• Cariprazine ^{[34] [99]}
• Chlorpromazine
• Clozapine ^{[67] [34]}
• Cyproheptadine
• Desmethylclozapine (NDMC; norclozapine)
• Ibogainalog ^[100]
• ITI-1549 ^[101]
• KB-128 – 5-HT_2A and 5-HT_2B antagonist and 5-HT_2C agonist ^[102]
• Lisuride – a dopamine agonist of the ergoline class, that is also a 5-HT_2B antagonist ^[103] and a dual 5-HT_2A/C agonist ^[104]
• Lurasidone
• LY-53857
• Mesulergine ^[67]
• Metadoxine – a 5-HT_2B antagonist and GABA-activity modulator ^[105]
• Metergoline ^[67]
• Metitepine (methiothepin) ^[67]
• Mianserin ^[67]
• Molindone ^{[106] [107]}
• N-Methylamisulpride
• Nantenine ^[74]
• Naphthylpiperazine (1-NP)
• Olanzapine
• Pimethixene ^[77]
• Pipamperone
• Pizotifen (pizotyline)
• Promethazine ^[108]
• Quetiapine
• Rauwolscine ^[34]
• Risperidone
• Ritanserin ^{[34] [67]}
• SB-200,646 – 5-HT_2B/5-HT_2C antagonist, selective over 5-HT_2A
• SB-206,553 – mixed 5-HT_2B and 5-HT_2C antagonist and PAM at α₇ nAChR ^{[76] [109] [110] [67]}
• SB-221,284 – 5-HT_2B/5-HT_2C antagonist ^{[38] [67]}
• SB-228,357 – 5-HT_2B/5-HT_2C antagonist
• SDZ SER-082 – a mixed 5-HT_2B/C antagonist
• Spiperone
• Tabernanthalog (TBG; DLX-007) ^[100]
• Tegaserod – primarily a 5-HT₄ agonist, but also a 5-HT_2B antagonist ^{[111] [112]}
• Terguride – an oral, potent antagonist of 5-HT_2A and 5-HT_2B receptors ^{[76] [34]}
• Trazodone ^[67]
• Vabicaserin ^[113]
• Viloxazine – weak 5-HT_2B antagonist and 5-HT_2C agonist ^{[114] [115]}
• Xanomeline – similar affinity as for muscarinic acetylcholine receptors ^{[91] [116] [117]}
• Yohimbine ^[34]
• Ziprasidone

Unknown or unsorted selectivity

• AM1030 (AM-1030) ^{[74] [118]}

Peripherally selective

• Sarpogrelate (MCI-9042, LS-187,118) – non-selective 5-HT₂ antagonist, but ~2 orders of magnitude lower affinity at 5-HT_2B than at 5-HT_2A ^{[119] [120]}
• VU0530244 – 5-HT_2B-selective ^[121]
• VU0631019 – 5-HT_2B-selective ^[121]
• VU6055320 – 5-HT_2B-selective ^{[91] [92]}

BW-501C67 and xylamidine are known peripherally selective antagonists of the serotonin 5-HT₂ receptors, including of the serotonin 5-HT_2A and 5-HT_2B receptors, but their serotonin 5-HT_2B receptor interactions do not appear to have been described. ^{[122] [123] [124]}

Possible applications

5-HT_2B 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. ^[125] More recent research has focused on possible application of 5-HT_2B antagonists as treatments for chronic heart disease. ^{[126] [127]} Research claims serotonin 5-HT_2B receptors have effect on liver regeneration. ^[128] Antagonism of 5-HT_2B may attenuate fibrogenesis and improve liver function in disease models in which fibrosis is pre-established and progressive.

See also

• 5-HT receptor

References

1. GRCh38: Ensembl release 89: ENSG00000135914 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000026228 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: HTR_2B 5-hydroxytryptamine (serotonin) receptor 2B".
6. Schmuck K, Ullmer C, Engels P, Lübbert H (Mar 1994). "Cloning and functional characterization of the human 5-HT2B serotonin receptor". FEBS Letters. 342 (1): 85–90. Bibcode:1994FEBSL.342...85S. doi: 10.1016/0014-5793(94)80590-3 . PMID   8143856. S2CID   11232259.
7. Frazer A, Hensler HG (1999). "Serotonin". Basic Neurochemistry: Molecular, Cellular and Medical Aspects (6th ed.). Lippincott-Raven.
8. Bonhaus DW, Bach C, DeSouza A, Salazar FH, Matsuoka BD, Zuppan P, et al. (June 1995). "The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors". British Journal of Pharmacology. 115 (4): 622–8. doi:10.1111/j.1476-5381.1995.tb14977.x. PMC   1908489 . PMID   7582481.
9. Enna SJ, Bylund DB, eds. (2008). XPharm : the comprehensive pharmacology reference. Amsterdam: Elsevier. ISBN   978-0-08-055232-3. OCLC   712018683.
10. Doly S, Valjent E, Setola V, Callebert J, Hervé D, Launay JM, et al. (Mar 2008). "Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro". The Journal of Neuroscience. 28 (11): 2933–40. doi:10.1523/JNEUROSCI.5723-07.2008. PMC   6670669 . PMID   18337424.
11. Launay JM, Hervé P, Peoc'h K, Tournois C, Callebert J, Nebigil CG, et al. (Oct 2002). "Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension" (PDF). Nature Medicine. 8 (10): 1129–35. doi:10.1038/nm764. PMID   12244304. S2CID   20736218.
12. Nebigil CG, Hickel P, Messaddeq N, Vonesch JL, Douchet MP, Monassier L, et al. (Jun 2001). "Ablation of serotonin 5-HT(2B) receptors in mice leads to abnormal cardiac structure and function". Circulation. 103 (24): 2973–9. doi: 10.1161/01.cir.103.24.2973 . PMID   11413089.
13. Elangbam CS, Job LE, Zadrozny LM, Barton JC, Yoon LW, Gates LD, et al. (Aug 2008). "5-hydroxytryptamine (5HT)-induced valvulopathy: compositional valvular alterations are associated with 5HT2B receptor and 5HT transporter transcript changes in Sprague-Dawley rats". Experimental and Toxicologic Pathology. 60 (4–5): 253–62. Bibcode:2008EToxP..60..253E. doi:10.1016/j.etp.2008.03.005. PMID   18511249.
14. Padhariya K, Bhandare R, Canney D, Velingkar V (2017-12-12). "Cardiovascular Concern of 5-HT2B Receptor and Recent Vistas in the Development of Its Antagonists". Cardiovascular & Hematological Disorders Drug Targets. 17 (2): 86–104. doi:10.2174/1871529X17666170703115111. PMID   28676029.
15. Neugebauer V (2020). "Serotonin—pain modulation". Handbook of the Behavioral Neurobiology of Serotonin. Handbook of Behavioral Neuroscience. Vol. 31. Elsevier. pp. 309–320. doi:10.1016/b978-0-444-64125-0.00017-7. ISBN   9780444641250. S2CID   212837146.
16. Jaffré F, Callebert J, Sarre A, Etienne N, Nebigil CG, Launay JM, et al. (Aug 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. doi: 10.1161/01.CIR.0000139856.20505.57 . PMID   15302781.
17. Monassier L, Laplante MA, Jaffré F, Bousquet P, Maroteaux L, de Champlain J (Aug 2008). "Serotonin 5-HT(2B) receptor blockade prevents reactive oxygen species-induced cardiac hypertrophy in mice". Hypertension. 52 (2): 301–7. doi: 10.1161/HYPERTENSIONAHA.107.105551 . PMID   18591460.
18. Jaffré F, Bonnin P, Callebert J, Debbabi H, Setola V, Doly S, et al. (Jan 2009). "Serotonin and angiotensin receptors in cardiac fibroblasts coregulate adrenergic-dependent cardiac hypertrophy". Circulation Research. 104 (1): 113–23. doi: 10.1161/CIRCRESAHA.108.180976 . PMID   19023134.
19. Callebert J, Esteve JM, Hervé P, Peoc'h K, Tournois C, Drouet L, et al. (May 2006). "Evidence for a control of plasma serotonin levels by 5-hydroxytryptamine(2B) receptors in mice" (PDF). The Journal of Pharmacology and Experimental Therapeutics. 317 (2): 724–31. doi:10.1124/jpet.105.098269. PMID   16461587. S2CID   16099098.
20. Diaz SL, Maroteaux L (Sep 2011). "Implication of 5-HT(2B) receptors in the serotonin syndrome". Neuropharmacology. 61 (3): 495–502. doi:10.1016/j.neuropharm.2011.01.025. PMID   21277875. S2CID   14905808.
21. Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, et al. (Dec 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. doi: 10.1161/01.CIR.102.23.2836 . PMID   11104741.
22. Fitzgerald LW, Burn TC, Brown BS, Patterson JP, Corjay MH, Valentine PA, et al. (Jan 2000). "Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine". Molecular Pharmacology. 57 (1): 75–81. doi:10.1016/S0026-895X(24)26444-0. PMID   10617681.
23. Roth BL (Jan 2007). "Drugs and valvular heart disease". The New England Journal of Medicine. 356 (1): 6–9. doi:10.1056/NEJMp068265. PMID   17202450.
24. "Archive: How Fen-Phen, a Diet 'Miracle,' Rose and Fell". archive.nytimes.com. Retrieved 2022-07-04.
25. Cavero I, Guillon JM (2014-03-01). "Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy". Journal of Pharmacological and Toxicological Methods. 69 (2): 150–161. doi:10.1016/j.vascn.2013.12.004. PMID   24361689.
26. PDB: 4IB4 ​; Wacker D, Wang C, Katritch V, Han GW, Huang XP, Vardy E, et al. (May 2013). "Structural features for functional selectivity at serotonin receptors". Science. 340 (6132): 615–9. Bibcode:2013Sci...340..615W. doi:10.1126/science.1232808. PMC   3644390 . PMID   23519215.
27. Schuhmacher M (2007). [Chiral arylmethoxytryptamines as 5-HT_2B-receptor antagonists: synthesis, analysis and in-vitro pharmacology] (German) (PDF) (Thesis). Ph.D. Dissertation. University of Regensburg. pp. 6–17. Archived from the original (PDF) on 2011-07-18. Retrieved 2008-08-11.
28. Amemiya N, Hatta S, Takemura H, Ohshika H (December 1996). "Characterization of the contractile response induced by 5-methoxytryptamine in rat stomach fundus strips". Eur J Pharmacol. 318 (2–3): 403–409. doi:10.1016/s0014-2999(96)00777-7. PMID   9016931.
29. Baxter GS, Murphy OE, Blackburn TP (May 1994). "Further characterization of 5-hydroxytryptamine receptors (putative 5-HT2B) in rat stomach fundus longitudinal muscle". Br J Pharmacol. 112 (1): 323–331. doi:10.1111/j.1476-5381.1994.tb13072.x. PMC   1910288 . PMID   8032658.
30. Luethi D, Liechti ME (2021). "Drugs of Abuse Affecting 5-HT2B Receptors". 5-HT2B Receptors. Vol. 35. Cham: Springer International Publishing. pp. 277–289. doi:10.1007/978-3-030-55920-5_16. ISBN   978-3-030-55919-9.
31. Cameron LP, Olson DE (October 2018). "Dark Classics in Chemical Neuroscience: N, N-Dimethyltryptamine (DMT)". ACS Chem Neurosci. 9 (10): 2344–2357. doi:10.1021/acschemneuro.8b00101. PMID   30036036.
32. Rickli A, Moning OD, Hoener MC, Liechti ME (August 2016). "Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens" (PDF). Eur Neuropsychopharmacol. 26 (8): 1327–1337. doi:10.1016/j.euroneuro.2016.05.001. PMID   27216487.
33. Tagen M, Mantuani D, van Heerden L, Holstein A, Klumpers LE, Knowles R (September 2023). "The risk of chronic psychedelic and MDMA microdosing for valvular heart disease". J Psychopharmacol. 37 (9): 876–890. doi:10.1177/02698811231190865. PMID   37572027.
34. Maroteaux L, Monassier L, Launay JM (2013). "Contribution of Serotonin 5-HT2B Receptors to Health and Disease". In Hall FS (ed.). Serotonin: Biosynthesis, Regulation and Health Implications. New York: Nova Science Publishers. ISBN   9781624176364.
35. Hutcheson JD, Setola V, Roth BL, Merryman WD (November 2011). "Serotonin receptors and heart valve disease--it was meant 2B". Pharmacol Ther. 132 (2): 146–157. doi:10.1016/j.pharmthera.2011.03.008. PMC   3179857 . PMID   21440001.
36. Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, et al. (September 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. doi:10.1038/sj.bjp.0702751. PMC   1571597 . PMID   10498829.
37. Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL (January 2013). "Neurochemical profiles of some novel psychoactive substances". Eur J Pharmacol. 700 (1–3): 147–151. doi:10.1016/j.ejphar.2012.12.006. PMC   3582025 . PMID   23261499.
38. Hoyer D (2019). "Serotonin receptors nomenclature". The Serotonin System. Elsevier. pp. 63–93. doi:10.1016/b978-0-12-813323-1.00004-9. ISBN   978-0-12-813323-1.
39. Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, et al. (Sep 1999). "Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells". British Journal of Pharmacology. 128 (1): 13–20. doi:10.1038/sj.bjp.0702751. PMC   1571597 . PMID   10498829.
40. Kennett GA, Trail B, Bright F (Dec 1998). "Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated". Neuropharmacology. 37 (12): 1603–10. doi:10.1016/S0028-3908(98)00115-4. PMID   9886683. S2CID   7310462.
41. McCorvy JD, Wacker D, Wang S, Agegnehu B, Liu J, Lansu K, et al. (August 2018). "Structural determinants of 5-HT2B receptor activation and biased agonism". Nature Structural & Molecular Biology. 25 (9): 787–796. doi:10.1038/s41594-018-0116-7. PMC   6237183 . PMID   30127358.
42. Jayakodiarachchi N, Maurer MA, Schultz DC, Dodd CJ, Thompson Gray A, Cho HP, et al. (January 2024). "Evaluation of the Indazole Analogs of 5-MeO-DMT and Related Tryptamines as Serotonin Receptor 2 Agonists". ACS Medicinal Chemistry Letters. 15 (2): 302–309. doi: 10.1021/acsmedchemlett.3c00566 . PMC   10860182 . PMID   38352850.
43. Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME (December 2015). "Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)" (PDF). Neuropharmacology. 99: 546–553. doi:10.1016/j.neuropharm.2015.08.034. PMID   26318099.
44. Barcelo B, Gomila I (2017). "Pharmacology and Literature Review Based on Related Death and Non-Fatal Case Reports of the Benzofurans and Benzodifurans Designer Drugs". Curr Pharm Des. 23 (36): 5523–5529. doi:10.2174/1381612823666170714155140. PMID   28714411.
45. Shimshoni JA, Winkler I, Golan E, Nutt D (January 2017). "Neurochemical binding profiles of novel indole and benzofuran MDMA analogues". Naunyn Schmiedebergs Arch Pharmacol. 390 (1): 15–24. doi:10.1007/s00210-016-1297-4. hdl: 10044/1/43622 . PMID   27650729.
46. May JA, Sharif NA, Chen HH, Liao JC, Kelly CR, Glennon RA, et al. (January 2009). "Pharmacological properties and discriminative stimulus effects of a novel and selective 5-HT2 receptor agonist AL-38022A [(S)-2-(8,9-dihydro-7H-pyrano[2,3-g]indazol-1-yl)-1-methylethylamine]". Pharmacol Biochem Behav. 91 (3): 307–314. doi:10.1016/j.pbb.2008.07.015. PMC   3763814 . PMID   18718483.
47. Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Curr Top Med Chem. 6 (17): 1845–1859. doi:10.2174/156802606778249766. PMID   17017961.
48. Rothman RB, Baumann MH (April 2002). "Serotonin releasing agents. Neurochemical, therapeutic and adverse effects". Pharmacol Biochem Behav. 71 (4): 825–836. doi:10.1016/s0091-3057(01)00669-4. PMID   11888573.
49. Cunningham MJ, Bock HA, Serrano IC, Bechand B, Vidyadhara DJ, Bonniwell EM, et al. (January 2023). "Pharmacological Mechanism of the Non-hallucinogenic 5-HT_2A Agonist Ariadne and Analogs". ACS Chemical Neuroscience. 14 (1): 119–135. doi:10.1021/acschemneuro.2c00597. PMC   10147382 . PMID   36521179.
50. Hoyer D (November 2020). "Targeting the 5-HT system: Potential side effects". Neuropharmacology. 179: 108233. doi:10.1016/j.neuropharm.2020.108233. PMID   32805212.
51. Isberg V, Paine J, Leth-Petersen S, Kristensen JL, Gloriam DE (2013). "Structure-activity relationships of constrained phenylethylamine ligands for the serotonin 5-HT2 receptors". PLOS ONE. 8 (11): e78515. Bibcode:2013PLoSO...878515I. doi: 10.1371/journal.pone.0078515 . PMC   3820707 . PMID   24244317.
52. Parker MA, Marona-Lewicka D, Lucaites VL, Nelson DL, Nichols DE (December 1998). "A novel (benzodifuranyl)aminoalkane with extremely potent activity at the 5-HT2A receptor". J Med Chem. 41 (26): 5148–5149. doi:10.1021/jm9803525. PMID   9857084.
53. Samson SL, Ezzat S (June 2014). "AACE/ACE Disease State Clinical Review: Dopamine Agonists for Hyperprolactinemia and the Risk of Cardiac Valve Disease". Endocr Pract. 20 (6): 608–616. doi:10.4158/EP14148.RA. PMID   24969114. Bromocriptine was first described as a 5HT-2BR antagonist (22) but was subsequently found to have partial agonist properties (23,24). [...] Regarding bromocriptine, there was no increased incidence of valve regurgitation in PD patients on bromocriptine in the population-based study of Schade et al (33), despite the significant findings for cabergoline and pergolide. However, there is a case report implicating high doses of bromocriptine as the cause of triple valve disease in a PD patient (37), and 1 study reported a significant correlation between cumulative dose of bromocriptine and the risk of valve regurgitation in a PD cohort (38). Other publications have reported fibrotic events, including retroperitoneal, pericardial and pleural fibrosis, in PD patients on high-dose bromocriptine (39-43). [...] Although there seems to be a lower risk of valvulopathy with bromocriptine, as a partial 5HT-2BR agonist, there still appears to be some risk with high-dose bromocriptine in PD patients.
54. Cavero I, Guillon JM (2014). "Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy". J Pharmacol Toxicol Methods. 69 (2): 150–161. doi:10.1016/j.vascn.2013.12.004. PMID   24361689.
55. Varty GB, Canal CE, Mueller TA, Hartsel JA, Tyagi R, Avery K, et al. (April 2024). "Synthesis and Structure-Activity Relationships of 2,5-Dimethoxy-4-Substituted Phenethylamines and the Discovery of CYB210010: A Potent, Orally Bioavailable and Long-Acting Serotonin 5-HT2 Receptor Agonist". Journal of Medicinal Chemistry. 67 (8): 6144–6188. doi:10.1021/acs.jmedchem.3c01961. PMID   38593423.
56. Palfreyman M, Varty G, Canal C, Hartsel J, Tyagi R, Avery K, et al. (December 2023). "ACNP 62nd Annual Meeting: Poster Abstracts P251 – P500: P405. Discovery and Preclinical Characterization of the Phenylalkylamine, CYB210010, a Potent and Long-Acting Serotonin 5-HT2A Receptor Agonist". Neuropsychopharmacology. 48 (Suppl 1): 211–354 (299–299. doi:10.1038/s41386-023-01756-4. PMC   10729596 . PMID   38040810.
57. Rothman RB, Baumann MH (May 2009). "Serotonergic drugs and valvular heart disease". Expert Opin Drug Saf. 8 (3): 317–329. doi:10.1517/14740330902931524. PMC   2695569 . PMID   19505264.
58. Nistala P (2018). "5-HT2B Receptor-mediated Cardiac Valvulopathy". VCU Theses and Dissertations. doi:10.25772/0YNR-6690.
59. Schaerlinger B, Hickel P, Etienne N, Guesnier L, Maroteaux L (September 2003). "Agonist actions of dihydroergotamine at 5-HT2B and 5-HT2C receptors and their possible relevance to antimigraine efficacy". Br J Pharmacol. 140 (2): 277–284. doi:10.1038/sj.bjp.0705437. PMC   1574033 . PMID   12970106.
60. Luethi D, Rudin D, Hoener MC, Liechti ME (2022). "Monoamine Receptor and Transporter Interaction Profiles of 4-Alkyl-Substituted 2,5-Dimethoxyamphetamines". The FASEB Journal. 36 (S1). doi: 10.1096/fasebj.2022.36.S1.R2691 . ISSN   0892-6638.
61. Huang XP, Setola V, Yadav PN, Allen JA, Rogan SC, Hanson BJ, et al. (Oct 2009). "Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment". Molecular Pharmacology. 76 (4): 710–22. doi:10.1124/mol.109.058057. PMC   2769050 . PMID   19570945.
62. "PDSP Ki database, University of North Carolina at Chapel Hill" . Retrieved 2019-09-04.
63. Wsół A (December 2023). "Cardiovascular safety of psychedelic medicine: current status and future directions". Pharmacol Rep. 75 (6): 1362–1380. doi:10.1007/s43440-023-00539-4. PMC   10661823 . PMID   37874530.
64. Brandt SD, Kavanagh PV, Twamley B, Westphal F, Elliott SP, Wallach J, et al. (February 2018). "Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775)". Drug Test Anal. 10 (2): 310–322. doi:10.1002/dta.2222. PMC   6230476 . PMID   28585392.
65. Setola V, Hufeisen SJ, Grande-Allen KJ, Vesely I, Glennon RA, Blough B, et al. (Jun 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. doi:10.1124/mol.63.6.1223. PMID   12761331. S2CID   839426.
66. Ray TS (2010). Manzoni OJ (ed.). "Psychedelics and the human receptorome". PLOS ONE. 5 (2): e9019. Bibcode:2010PLoSO...5.9019R. doi: 10.1371/journal.pone.0009019 . PMC   2814854 . PMID   20126400.
67. Knight AR, Misra A, Quirk K, Benwell K, Revell D, Kennett G, et al. (August 2004). "Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors". Naunyn Schmiedebergs Arch Pharmacol. 370 (2): 114–123. doi:10.1007/s00210-004-0951-4. PMID   15322733.
68. Rothman RB, Blough BE, Baumann MH (January 2007). "Dual dopamine/serotonin releasers as potential medications for stimulant and alcohol addictions". AAPS J. 9 (1): E1–10. doi:10.1208/aapsj0901001. PMC   2751297 . PMID   17408232.
69. Görnemann T, Hübner H, Gmeiner P, Horowski R, Latté KP, Flieger M, et al. (Mar 2008). "Characterization of the molecular fragment that is responsible for agonism of pergolide at serotonin 5-Hydroxytryptamine2B and 5-Hydroxytryptamine2A receptors". The Journal of Pharmacology and Experimental Therapeutics. 324 (3): 1136–45. doi:10.1124/jpet.107.133165. PMID   18096760. S2CID   24907300.
70. "AL-34662". Inxight Drugs. Retrieved 25 November 2024.
71. Luethi D, Kolaczynska KE, Docci L, Krähenbühl S, Hoener MC, Liechti ME (May 2018). "Pharmacological profile of mephedrone analogs and related new psychoactive substances" (PDF). Neuropharmacology. 134 (Pt A): 4–12. doi:10.1016/j.neuropharm.2017.07.026. PMID   28755886.
72. Rickli A, Kopf S, Hoener MC, Liechti ME (July 2015). "Pharmacological profile of novel psychoactive benzofurans". Br J Pharmacol. 172 (13): 3412–3425. doi:10.1111/bph.13128. PMC   4500375 . PMID   25765500.
73. Luethi D, Kolaczynska KE, Walter M, Suzuki M, Rice KC, Blough BE, et al. (July 2019). "Metabolites of the ring-substituted stimulants MDMA, methylone and MDPV differentially affect human monoaminergic systems". J Psychopharmacol. 33 (7): 831–841. doi:10.1177/0269881119844185. PMC   8269116 . PMID   31038382.
74. Wang Q, Zhou Y, Huang J, Huang N (January 2021). "Structure, Function, and Pharmaceutical Ligands of 5-Hydroxytryptamine 2B Receptor". Pharmaceuticals (Basel). 14 (2): 76. doi: 10.3390/ph14020076 . PMC   7909583 . PMID   33498477.
75. Kim M, Truss M, Pagare PP, Essandoh MA, Zhang Y, Williams DA (November 2020). "Structure activity relationship exploration of 5-hydroxy-2-(3-phenylpropyl)chromones as a unique 5-HT2B receptor antagonist scaffold". Bioorg Med Chem Lett. 30 (21): 127511. doi:10.1016/j.bmcl.2020.127511. PMID   32853682.
76. Brea J, Castro-Palomino J, Yeste S, Cubero E, Párraga A, Domínguez E, et al. (2010). "Emerging opportunities and concerns for drug discovery at serotonin 5-HT2B receptors". Curr Top Med Chem. 10 (5): 493–503. doi:10.2174/156802610791111524. PMID   20166944.
77. Schmitz B, Ullmer C, Segelcke D, Gwarek M, Zhu XR, Lübbert H (March 2015). "BF-1--a novel selective 5-HT2B receptor antagonist blocking neurogenic dural plasma protein extravasation in guinea pigs". Eur J Pharmacol. 751: 73–80. doi:10.1016/j.ejphar.2015.01.043. PMID   25666387.
78. Kovács A, Gacsályi I, Wellmann J, Schmidt E, Szücs Z, Dubreuil V, et al. (2003). "Effects of EGIS-7625, a selective and competitive 5-HT2B receptor antagonist". Cardiovasc Drugs Ther. 17 (5–6): 427–434. doi:10.1023/b:card.0000015857.96371.43. PMID   15107597.
79. Kovács A, Gacsályi I, Wellmann J, Schmidt E, Szücs Z, Dubreuil V, et al. (2003). "Effects of EGIS-7625, a selective and competitive 5-HT2B receptor antagonist". Cardiovascular Drugs and Therapy. 17 (5–6): 427–34. doi:10.1023/B:CARD.0000015857.96371.43. PMID   15107597. S2CID   11532969.
80. Löfdahl A, Rydell-Törmänen K, Müller C, Martina Holst C, Thiman L, Ekström G, et al. (August 2016). "5-HT2B receptor antagonists attenuate myofibroblast differentiation and subsequent fibrotic responses in vitro and in vivo". Physiol Rep. 4 (15). doi:10.14814/phy2.12873. PMC   4985542 . PMID   27482070.
81. Glennon RA, Dukat M (2012). "Serotonin Receptors and Drugs Affecting Serotonergic Neurotransmission". Foye's Textbook of Medical Chemistry (PDF) (7 ed.). Baltimore: Williams and Wilkins Inc. pp. 315–337. ISBN   9781609133450.
82. van Wijngaarden I, Soudijn W (1997). "5-HT2A, 5-HT2B and 5-HT2C receptor ligands". Pharmacochemistry Library. Vol. 27. Elsevier. pp. 161–197. doi:10.1016/s0165-7208(97)80013-x. ISBN   978-0-444-82041-9.
83. Tosh DK, Calkins MM, Ivancich MS, Bock HA, Campbell RG, Lewicki SA, et al. (November 2023). "Structure activity relationships of 5-HT2B and 5-HT2C serotonin receptor antagonists: N6, C2 and 5'-Modified (N)-methanocarba-adenosine derivatives". Eur J Med Chem. 259: 115691. doi:10.1016/j.ejmech.2023.115691. PMC   10529765 . PMID   37562117.
84. Tosh DK, Pavan M, Clark AA, Lammers J, Villano S, Marri S, et al. (November 2024). "Potent and Selective Human 5-HT2B Serotonin Receptor Antagonists: 4'-Cyano-(N)-methanocarba-adenosines by Synthetic Serendipity". J Med Chem. 67 (23): 21264–21291. doi:10.1021/acs.jmedchem.4c02174. PMID   39589936.
85. Acquarone E, Argyrousi EK, Arancio O, Watterson DM, Roy SM (2024). "The 5HT2b Receptor in Alzheimer's Disease: Increased Levels in Patient Brains and Antagonist Attenuation of Amyloid and Tau Induced Dysfunction". J Alzheimers Dis. 98 (4): 1349–1360. doi:10.3233/JAD-240063. PMC   11091653 . PMID   38578894.
86. Takahashi N, Inagaki K, Taniguchi K, Sakaguchi Y, Kawamura K (2011). "The Novel 5-HT2B Receptor Antagonist, RQ-00310941, Attenuates Visceral Hypersensitivity and Abnormal Defecation in Rat Models". Gastroenterology. 140 (5): S–607. doi: 10.1016/S0016-5085(11)62513-4 .
87. Name D (17 April 2024). "RQ 00310941". AdisInsight. Retrieved 30 November 2024.
88. Bonhaus DW, Flippin LA, Greenhouse RJ, Jaime S, Rocha C, Dawson M, et al. (Jul 1999). "RS-127445: a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist". British Journal of Pharmacology. 127 (5): 1075–82. doi:10.1038/sj.bjp.0702632. PMC   1566110 . PMID   10455251.
89. Forbes IT, Jones GE, Murphy OE, Holland V, Baxter GS (March 1995). "N-(1-methyl-5-indolyl)-N'-(3-methyl-5-isothiazolyl)urea: a novel, high-affinity 5-HT2B receptor antagonist". Journal of Medicinal Chemistry. 38 (6): 855–857. doi:10.1021/jm00006a001. PMID   7699699.
90. Reavill C, Kettle A, Holland V, Riley G, Blackburn TP (Feb 1999). "Attenuation of haloperidol-induced catalepsy by a 5-HT2C receptor antagonist". British Journal of Pharmacology. 126 (3): 572–4. doi:10.1038/sj.bjp.0702350. PMC   1565856 . PMID   10188965.
91. Bender AM, Parr LC, Livingston WB, Lindsley CW, Merryman WD (August 2023). "2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery". J Med Chem. 66 (16): 11027–11039. doi:10.1021/acs.jmedchem.3c01178. PMC   11073569 . PMID   37584406.
92. Valentine MS, Bender AM, Shay S, Paffenroth KC, Gladson S, Dickerson JW, et al. (October 2023). "Development of a Peripherally Restricted 5-HT2B Partial Agonist for Treatment of Pulmonary Arterial Hypertension". JACC Basic Transl Sci. 8 (10): 1379–1388. doi:10.1016/j.jacbts.2023.06.014. PMC   10714182 . PMID   38094686.
93. Lewis V, Bonniwell EM, Lanham JK, Ghaffari A, Sheshbaradaran H, Cao AB, et al. (March 2023). "A non-hallucinogenic LSD analog with therapeutic potential for mood disorders". Cell Rep. 42 (3): 112203. doi:10.1016/j.celrep.2023.112203. PMC   10112881 . PMID   36884348.
94. Canal CE, Morgan D, Felsing D, Kondabolu K, Rowland NE, Robertson KL, et al. (May 2014). "A novel aminotetralin-type serotonin (5-HT) 2C receptor-specific agonist and 5-HT2A competitive antagonist/5-HT2B inverse agonist with preclinical efficacy for psychoses". J Pharmacol Exp Ther. 349 (2): 310–318. doi:10.1124/jpet.113.212373. PMC   3989798 . PMID   24563531.
95. Rasmussen K, Engel S, Chytil M, Koenig A, Meyer R, Rus M, et al. (December 2023). "ACNP 62nd Annual Meeting: Poster Abstracts P251 - P500: P361. Preclinical Pharmacology of DLX-001, a Novel Non-Hallucinogenic Neuroplastogen With the Potential for Treating Neuropsychiatric Diseases". Neuropsychopharmacology. 48 (Suppl 1): 211–354 (274–275). doi:10.1038/s41386-023-01756-4. PMC   10729596 . PMID   38040810.
96. Millan MJ, Gobert A, Lejeune F, Dekeyne A, Newman-Tancredi A, Pasteau V, et al. (Sep 2003). "The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways". The Journal of Pharmacology and Experimental Therapeutics. 306 (3): 954–64. doi:10.1124/jpet.103.051797. PMID   12750432. S2CID   18753440.
97. "Delving into the Latest Updates on AMAP-102 with Synapse". Synapse. 21 November 2024. Retrieved 30 November 2024.
98. Vasilkevich A, Duan J, Lovera A, McCorvy J, Pedersen JT (October 2024). Novel 5-HT2A/2C mixed and partial agonist and its efficacy in preclinical pain models (PDF). Society for Neuroscience 2024 Annual Meeting, Chicago, October 5-9.
99. Garnock-Jones KP (June 2017). "Cariprazine: A Review in Schizophrenia". CNS Drugs. 31 (6): 513–525. doi:10.1007/s40263-017-0442-z. PMID   28560619. S2CID   4392274.
100. Cameron LP, Tombari RJ, Lu J, Pell AJ, Hurley ZQ, Ehinger Y, et al. (January 2021). "A non-hallucinogenic psychedelic analogue with therapeutic potential". Nature. 589 (7842): 474–479. Bibcode:2021Natur.589..474C. doi:10.1038/s41586-020-3008-z. PMC   7874389 . PMID   33299186.
101. Davis R, Dutheil SS, Zhang L, Lehmann E, Awadallah N, Yao W, et al. (December 2023). "ACNP 62nd Annual Meeting: Poster Abstracts P251 - P500: P358. Discovery and Characterization of ITI-1549, a Novel Non-Hallucinogenic Psychedelic for the Treatment of Neuropsychiatric Disorders". Neuropsychopharmacology. 48 (Suppl 1): 211–354 (272–273). doi:10.1038/s41386-023-01756-4. PMC   10729596 . PMID   38040810.
102. "Küleon Bioscience Announces Scientific Breakthrough with First Known Trifunctional 5-HT2C Receptor Agonist that is also a Full Antagonist of the 5-HT2A and 5-HT2B Receptors, Creating an Exciting Lead for Multiple Neuropsychiatric Illnesses". BioSpace. 5 October 2023. Retrieved 30 November 2024.
103. Hofmann C, Penner U, Dorow R, Pertz HH, Jähnichen S, Horowski R, et al. (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". Clinical Neuropharmacology. 29 (2): 80–6. doi:10.1097/00002826-200603000-00005. PMID   16614540. S2CID   33849447.
104. Egan CT, Herrick-Davis K, Miller K, Glennon RA, Teitler M (Apr 1998). "Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors". Psychopharmacology. 136 (4): 409–14. doi:10.1007/s002130050585. PMID   9600588. S2CID   3021798.
105. "Metadoxine extended release (MDX) for adult ADHD". Alcobra Ltd. 2014. Archived from the original on 2019-02-13. Retrieved 2014-05-07.
106. Robb AS, Schwabe S, Ceresoli-Borroni G, Nasser A, Yu C, Marcus R, et al. (March 2019). "A proposed anti-maladaptive aggression agent classification: improving our approach to treating impulsive aggression". Postgrad Med. 131 (2): 129–137. doi: 10.1080/00325481.2019.1574401 . PMID   30678534.
107. Yu C, Gopalakrishnan G (2018). "In vitro pharmacological characterization of SPN-810M (molindone)". J Exp Pharmacol. 10: 65–73. doi: 10.2147/JEP.S180777 . PMC   6254985 . PMID   30538587.
108. "promethazine | Activity data visualisation tool | IUPHAR/BPS Guide to PHARMACOLOGY". www.guidetopharmacology.org. Retrieved 2019-02-28.
109. Kennett GA, Wood MD, Bright F, Cilia J, Piper DC, Gager T, et al. (February 1996). "In vitro and in vivo profile of SB 206553, a potent 5-HT2C/5-HT2B receptor antagonist with anxiolytic-like properties". Br J Pharmacol. 117 (3): 427–434. doi:10.1111/j.1476-5381.1996.tb15208.x. PMC   1909304 . PMID   8821530.
110. Dunlop J, Lock T, Jow B, Sitzia F, Grauer S, Jow F, et al. (Mar 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)". The Journal of Pharmacology and Experimental Therapeutics. 328 (3): 766–776. doi:10.1124/jpet.108.146514. PMID   19050173. S2CID   206500076.
111. Beattie DT, Smith JA, Marquess D, Vickery RG, Armstrong SR, Pulido-Rios T, et al. (Nov 2004). "The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo". British Journal of Pharmacology. 143 (5): 549–560. doi:10.1038/sj.bjp.0705929. PMC   1575425 . PMID   15466450.
112. McCullough JL, Armstrong SR, Hegde SS, Beattie DT (April 2006). "The 5-HT2B antagonist and 5-HT4 agonist activities of tegaserod in the anaesthetized rat". Pharmacol Res. 53 (4): 353–358. doi:10.1016/j.phrs.2006.01.003. PMID   16495076.
113. Dunlop J, Watts SW, Barrett JE, Coupet J, Harrison B, Mazandarani H, et al. (June 2011). "Characterization of vabicaserin (SCA-136), a selective 5-hydroxytryptamine 2C receptor agonist". J Pharmacol Exp Ther. 337 (3): 673–680. doi:10.1124/jpet.111.179572. PMID   21402690.
114. Yu C, Garcia-Olivares J, Candler S, Schwabe S, Maletic V (2020). "New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties". Journal of Experimental Pharmacology. 12: 285–300. doi: 10.2147/JEP.S256586 . PMC   7473988 . PMID   32943948.
115. Garcia-Olivares J, Yegla B, Earnest J, Maletic V, Yu C (2023). "Characterization of Viloxazine Effects on Cortical Serotonin Neurotransmission at Doses Relevant for ADHD Treatment". CNS Spectrums. 28 (2): 235. doi: 10.1017/S1092852923001633 . ISSN   1092-8529.
116. Watson J, Brough S, Coldwell MC, Gager T, Ho M, Hunter AJ, et al. (December 1998). "Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors". Br J Pharmacol. 125 (7): 1413–1420. doi:10.1038/sj.bjp.0702201. PMC   1565721 . PMID   9884068.
117. Odagaki Y, Kinoshita M, Ota T (September 2016). "Comparative analysis of pharmacological properties of xanomeline and N-desmethylclozapine in rat brain membranes". J Psychopharmacol. 30 (9): 896–912. doi:10.1177/0269881116658989. PMID   27464743.
118. "Delving into the Latest Updates on AM-1030 with Synapse". Synapse. 21 November 2024. Retrieved 30 November 2024.
119. Rashid M, Manivet P, Nishio H, Pratuangdejkul J, Rajab M, Ishiguro M, et al. (May 2003). "Identification of the binding sites and selectivity of sarpogrelate, a novel 5-HT2 antagonist, to human 5-HT2A, 5-HT2B and 5-HT2C receptor subtypes by molecular modeling". Life Sci. 73 (2): 193–207. doi:10.1016/s0024-3205(03)00227-3. PMID   12738034.
120. Muntasir HA, Hossain M, Bhuiyan MA, Komiyama T, Nakamura T, Ozaki M, et al. (July 2007). "Identification of a key amino acid of the human 5-HT(2B) serotonin receptor important for sarpogrelate binding". J Pharmacol Sci. 104 (3): 274–277. doi:10.1254/jphs.sc0060241. PMID   17609583.
121. Bender AM, Valentine MS, Bauer JA, Days E, Lindsley CW, Merryman WD (April 2023). "Identification of Potent, Selective, and Peripherally Restricted Serotonin Receptor 2B Antagonists from a High-Throughput Screen". Assay Drug Dev Technol. 21 (3): 89–96. doi:10.1089/adt.2022.116. PMC   10122230 . PMID   36930852.
122. Chaouloff F, Layeillon C, Baudrie V (January 1993). "5-HT1C/5-HT2 receptor blockade prevents 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane-, but not stress-induced increases in brain tryptophan". European Journal of Pharmacology. 231 (1): 77–82. doi:10.1016/0014-2999(93)90686-c. PMID   8095238.
123. Glennon RA, Westkaemper RB (1992). "Serotonin Receptors, 5-th Ligands and Receptor Modeling". Pharmacochemistry Library. Vol. 18. Elsevier. pp. 185–207. doi:10.1016/b978-0-444-88931-7.50017-7. ISBN   978-0-444-88931-7. Various polycyclic agents such as butaclamol, mianserin, cyproheptadine, pizotyline bind at 5-HT2 receptors with high affinity. These agents are not selective and bind with comparable affinty either at other populations of 5-HT receptors or at other neurotransmitter receptors. Other, structurally unique agents have also been investigated including cinanserin and xylamidine. The latter compound has seen application as a peripheral 5-HT2 antagonist in that it does not readily penetrate the blood-brain barrier; however, xylamidine binds equally well at 5-HTIC and 5-HT2 receptors. See references 3 and 5 for additional information on these types of agents.
124. Dave KD, Quinn JL, Harvey JA, Aloyo VJ (March 2004). "Role of central 5-HT2 receptors in mediating head bobs and body shakes in the rabbit". Pharmacol Biochem Behav. 77 (3): 623–629. doi:10.1016/j.pbb.2003.12.017. PMID   15006475. Systemic administration of the peripheral 5-HT2A/2C antagonist xylamidine [...] First, systemic injections of the peripherally acting 5-HT2A/2C receptor antagonist xylamidine were employed to study its effects on head bobs and body shakes produced by systemic injections of DOI.
125. Poissonnet G, Parmentier JG, Boutin JA, Goldstein S (Mar 2004). "The emergence of selective 5-HT 2B antagonists structures, activities and potential therapeutic applications". Mini Reviews in Medicinal Chemistry. 4 (3): 325–30. doi:10.2174/1389557043487312. PMID   15032678.
126. Shyu KG (Jan 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. doi:10.1161/CIRCRESAHA.108.191122. PMID   19118279. S2CID   41931843.
127. Moss N, Choi Y, Cogan D, Flegg A, Kahrs A, Loke P, et al. (Apr 2009). "A new class of 5-HT2B antagonists possesses favorable potency, selectivity, and rat pharmacokinetic properties". Bioorganic & Medicinal Chemistry Letters. 19 (8): 2206–10. doi:10.1016/j.bmcl.2009.02.126. PMID   19307114.
128. Ebrahimkhani MR, Oakley F, Murphy LB, Mann J, Moles A, Perugorria MJ, et al. (Dec 2011). "Stimulating healthy tissue regeneration by targeting the 5-HT₂B receptor in chronic liver disease". Nature Medicine. 17 (12): 1668–73. doi:10.1038/nm.2490. PMC   3428919 . PMID   22120177.

Further reading

• Raymond JR, Mukhin YV, Gelasco A, Turner J, Collinsworth G, Gettys TW, et al. (2002). "Multiplicity of mechanisms of serotonin receptor signal transduction". Pharmacology & Therapeutics. 92 (2–3): 179–212. doi:10.1016/S0163-7258(01)00169-3. PMID   11916537.
• Choi DS, Birraux G, Launay JM, Maroteaux L (Oct 1994). "The human serotonin 5-HT2B receptor: pharmacological link between 5-HT2 and 5-HT1D receptors". FEBS Letters. 352 (3): 393–9. Bibcode:1994FEBSL.352..393C. doi:10.1016/0014-5793(94)00968-6. PMID   7926008. S2CID   26931598.
• Kursar JD, Nelson DL, Wainscott DB, Baez M (Aug 1994). "Molecular cloning, functional expression, and mRNA tissue distribution of the human 5-hydroxytryptamine2B receptor". Molecular Pharmacology. 46 (2): 227–34. PMID   8078486.
• Schmuck K, Ullmer C, Engels P, Lübbert H (Mar 1994). "Cloning and functional characterization of the human 5-HT2B serotonin receptor". FEBS Letters. 342 (1): 85–90. Bibcode:1994FEBSL.342...85S. doi: 10.1016/0014-5793(94)80590-3 . PMID   8143856. S2CID   11232259.
• Launay JM, Birraux G, Bondoux D, Callebert J, Choi DS, Loric S, et al. (Feb 1996). "Ras involvement in signal transduction by the serotonin 5-HT2B receptor". The Journal of Biological Chemistry. 271 (6): 3141–7. doi: 10.1074/jbc.271.6.3141 . PMID   8621713.
• Le Coniat M, Choi DS, Maroteaux L, Launay JM, Berger R (Feb 1996). "The 5-HT2B receptor gene maps to 2q36.3-2q37.1" (PDF). Genomics. 32 (1): 172–3. doi:10.1006/geno.1996.0101. PMID   8786115.
• Kim SJ, Veenstra-VanderWeele J, Hanna GL, Gonen D, Leventhal BL, Cook EH (Feb 2000). "Mutation screening of human 5-HT(2B)receptor gene in early-onset obsessive-compulsive disorder". Molecular and Cellular Probes. 14 (1): 47–52. doi:10.1006/mcpr.1999.0281. PMID   10722792.
• Manivet P, Mouillet-Richard S, Callebert J, Nebigil CG, Maroteaux L, Hosoda S, et al. (Mar 2000). "PDZ-dependent activation of nitric-oxide synthases by the serotonin 2B receptor". The Journal of Biological Chemistry. 275 (13): 9324–31. doi: 10.1074/jbc.275.13.9324 . PMID   10734074.
• Becamel C, Figge A, Poliak S, Dumuis A, Peles E, Bockaert J, et al. (Apr 2001). "Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1". The Journal of Biological Chemistry. 276 (16): 12974–82. doi: 10.1074/jbc.M008089200 . PMID   11150294.
• Manivet P, Schneider B, Smith JC, Choi DS, Maroteaux L, Kellermann O, et al. (May 2002). "The serotonin binding site of human and murine 5-HT2B receptors: molecular modeling and site-directed mutagenesis". The Journal of Biological Chemistry. 277 (19): 17170–8. doi: 10.1074/jbc.M200195200 . PMID   11859080.
• Borman RA, Tilford NS, Harmer DW, Day N, Ellis ES, Sheldrick RL, et al. (Mar 2002). "5-HT(2B) receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro". British Journal of Pharmacology. 135 (5): 1144–51. doi:10.1038/sj.bjp.0704571. PMC   1573235 . PMID   11877320.
• Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, et al. (May 2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways". Oncogene. 22 (21): 3307–18. doi:10.1038/sj.onc.1206406. PMID   12761501. S2CID   38880905.
• Slominski A, Pisarchik A, Zbytek B, Tobin DJ, Kauser S, Wortsman J (Jul 2003). "Functional activity of serotoninergic and melatoninergic systems expressed in the skin". Journal of Cellular Physiology. 196 (1): 144–53. doi: 10.1002/jcp.10287 . PMID   12767050. S2CID   24534729.
• Lin Z, Walther D, Yu XY, Drgon T, Uhl GR (Dec 2004). "The human serotonin receptor 2B: coding region polymorphisms and association with vulnerability to illegal drug abuse". Pharmacogenetics. 14 (12): 805–11. doi:10.1097/00008571-200412000-00003. PMID   15608559.

External links

• "5-HT_2B". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2017-02-02. Retrieved 2008-11-25.
• Human HTR2B genome location and HTR2B gene details page in the UCSC Genome Browser .
• Overview of all the structural information available in the PDB for UniProt : P41595 (5-hydroxytryptamine receptor 2B) at the PDBe-KB .

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