5-HT2B receptor
5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene.[5][6] 5-HT2B 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-HT2B receptor is Gq/G11-protein coupled, leading to downstream activation of phospholipase C.
Tissue distribution and function
[edit]First discovered in the stomach of rats, 5-HT2B was challenging to characterize initially because of its structural similarity to the other 5-HT2 receptors, particularly 5-HT2C.[7] 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 (CNS) effects include neuronal sensitization to tactile stimuli and mediation of some of the effects of hallucinogenic substituted amphetamines. The 5-HT2B 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-HT2B receptor subtype is involved in:
- CNS: inhibition of serotonin and dopamine uptake, behavioral effects[10]
- Vascular: pulmonary vasoconstriction[11]
- Cardiac: The 5-HT2B receptor regulates cardiac structure and functions, as demonstrated by the abnormal cardiac development observed in 5-HT2B 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-HT2B receptors were discovered to prevent both angiotensin II or beta-adrenergic agonist-induced pathological cardiac hypertrophy in mouse.[16][17][18]
- 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,[19] and with the abnormal acute serotonin release produced by drugs such as MDMA.[10] Surprisingly, however, 5-HT2B 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
[edit]5-HT2B 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-HT2B stimulation.[24] Today, 5-HT2B agonism is considered a toxicity signal precluding further clinical development of a compound.[25]
Ligands
[edit]The structure of the 5-HT2B receptor was resolved in a complex with the valvulopathogenic drug ergotamine.[26] 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.[27]
Agonists
[edit]Endogenous
[edit]- 5-Methoxytryptamine (5-MT) – trace amine[28][29]
- DMT – trace amine[30][31][32][33]
- Serotonin – neurotransmitter, KD ≈ 10 nM[34][35][36]
- Tryptamine – trace amine[34][36]
Selective
[edit]- 6-APB – ~100-fold selectivity over the 5-HT2A and 5-HT2C receptors, ≥32-fold selectivity over monoamine release, ~12-fold selectivity over α2C-adrenergic receptor[30][37]
- α-Methylserotonin – ~10-fold selectivity over 5-HT2A and 5-HT2C[34][38][36]
- BW-723C86 – 100-fold selectivity over 5-HT2A but only 3- to 10-fold selectivity over 5-HT2C,[34][39] fair functional subtype selectivity, almost full agonist, anxiolytic in vivo[40]
- LY-266,097 – biased partial agonist in favor of Gq protein, no β-arrestin2 recruitment[41]
- VU6067416 – modest selectivity over 5-HT2A and 5-HT2C[42]
Non-selective
[edit]- 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 α2A-adrenergic agonist, but has 5-HT2B agonistic activity at therapeutic concentrations[35][61]
- Levofenfluramine[57]
- Levonorfenfluramine[57]
- Lorcaserin[54]
- LSD – about equal affinity for human cloned 5-HT2B and 5-HT2A 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-HT2A, potent agonist at both 5-HT2B/C[34][39]
- Ropinirole[35]
- Quinidine[35]
- TFMPP (weak partial agonist)[36]
- VER-3323 – mixed 5-HT2C and 5-HT2B agonist with weaker 5-HT2A affinity[67]
- Xylometazoline[35]
Peripherally selective
[edit]Inactive
[edit]A number of notable drugs appear to be inactive or very weak as serotonin 5-HT2B 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-HT2B receptor agonists.[63][30][32]
Antagonists
[edit]Selective
[edit]- 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-HT2A[76][78][79]
- EXT5 – highly selective[74][80]
- EXT9 – somewhat selective[74][80]
- LY-23,728[81]
- LY-266,097 – pKi = 9.7, 100-fold selectivity over 5-HT2A and 5-HT2C[34][81]
- LY-272,015 – fairly selective and highly potent[34]
- LY-287,375[81][82]
- MRS7925 – substantially selective over 5-HT2A and 5-HT2C but minimal selectivity over the adenosine A1 receptor[83]
- MRS8209[84]
- MW071 (MW01-8-071HAB) – non-MAOI minaprine analogue[85]
- PRX-08066 – Ki ≈ 1.7 nM, >100-fold selectivity[74][76][34]
- RQ-00310941 (RQ-941) – Ki = 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) – Ki = 0.3 nM, >1,000-fold selectivity over 5-HT2A and 5-HT2C 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-HT2C and 5-HT2A[89]
- SB-215,505 – mixed 5-HT2B and 5-HT2C antagonist[34][76][90]
- VU6047534 – weak partial agonist or antagonist, peripherally selective in mice but not humans[91][92]
Non-selective
[edit]- 2-Bromo-LSD (BOL-148; bromolysergide)[93]
- (–)-MBP – 5-HT2A antagonist, 5-HT2B inverse agonist, and 5-HT2C agonist[94]
- AAZ-A-154 (DLX-001)[95]
- Agomelatine – primarily a melatonin MT1/MT2 receptor agonist, with a less potent antagonism of 5-HT2B and 5-HT2C[96]
- AMAP102 (AMAP-102) – 5-HT2B and 5-HT2C 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-HT2A and 5-HT2B antagonist and 5-HT2C agonist[102]
- Lisuride – a dopamine agonist of the ergoline class, that is also a 5-HT2B antagonist[103] and a dual 5-HT2A/C agonist[104]
- Lurasidone
- LY-53857
- Mesulergine[67]
- Metadoxine – a 5-HT2B 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-HT2B/5-HT2C antagonist, selective over 5-HT2A
- SB-206,553 – mixed 5-HT2B and 5-HT2C antagonist and PAM at α7 nAChR[76][109][110][67]
- SB-221,284 – 5-HT2B/5-HT2C antagonist[38][67]
- SB-228,357 – 5-HT2B/5-HT2C antagonist
- SDZ SER-082 – a mixed 5-HT2B/C antagonist
- Spiperone
- Tabernanthalog (TBG; DLX-007)[100]
- Tegaserod – primarily a 5-HT4 agonist, but also a 5-HT2B antagonist[111][112]
- Terguride – an oral, potent antagonist of 5-HT2A and 5-HT2B receptors[76][34]
- Trazodone[67]
- Vabicaserin[113]
- Viloxazine – weak 5-HT2B antagonist and 5-HT2C agonist[114][115]
- Xanomeline – similar affinity as for muscarinic acetylcholine receptors[91][116][117]
- Yohimbine[34]
- Ziprasidone
Unknown or unsorted selectivity
[edit]Peripherally selective
[edit]- Sarpogrelate (MCI-9042, LS-187,118) – non-selective 5-HT2 antagonist, but ~2 orders of magnitude lower affinity at 5-HT2B than at 5-HT2A[119][120]
- VU0530244 – 5-HT2B-selective[121]
- VU0631019 – 5-HT2B-selective[121]
- VU6055320 – 5-HT2B-selective[91][92]
BW-501C67 and xylamidine are known peripherally selective antagonists of the serotonin 5-HT2 receptors, including of the serotonin 5-HT2A and 5-HT2B receptors, but their serotonin 5-HT2B receptor interactions do not appear to have been described.[122][123][124]
Possible applications
[edit]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.[125] More recent research has focused on possible application of 5-HT2B antagonists as treatments for chronic heart disease.[126][127] Research claims serotonin 5-HT2B receptors have effect on liver regeneration.[128] Antagonism of 5-HT2B may attenuate fibrogenesis and improve liver function in disease models in which fibrosis is pre-established and progressive.
See also
[edit]References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000135914 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026228 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: HTR2B 5-hydroxytryptamine (serotonin) receptor 2B".
- ^ 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.
- ^ Frazer A, Hensler HG (1999). "Serotonin". Basic Neurochemistry: Molecular, Cellular and Medical Aspects (6th ed.). Lippincott-Raven.
- ^ 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.
- ^ Enna SJ, Bylund DB, eds. (2008). XPharm : the comprehensive pharmacology reference. Amsterdam: Elsevier. ISBN 978-0-08-055232-3. OCLC 712018683.
- ^ a b 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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. PMID 10617681.
- ^ 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.
- ^ "Archive: How Fen-Phen, a Diet 'Miracle,' Rose and Fell". archive.nytimes.com. Retrieved 2022-07-04.
- ^ 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.
- ^ 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.
- ^ Schuhmacher M (2007). [Chiral arylmethoxytryptamines as 5-HT2B-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.
- ^ 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.
- ^ 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.
- ^ a b c d e f g h i j k l m n o p q r s t u v w x y 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.
- ^ 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.
- ^ a b c d e f 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.
- ^ a b c 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.
- ^ a b c d e f g h i j k l m n o p q r s 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.
- ^ a b c d e f g h i j k l m n o 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.
- ^ a b c d e f g h i j 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.
- ^ a b c d 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.
- ^ a b 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.
- ^ a b c 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.
- ^ 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.
- ^ 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.
- ^ a b 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.
{{cite journal}}: CS1 maint: overridden setting (link) - ^ a b c d e f g 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.
- ^ a b 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.
- ^ a b c 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. PMID 27650729.
- ^ 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.
- ^ a b c 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.
- ^ 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.
- ^ Cunningham MJ, Bock HA, Serrano IC, Bechand B, Vidyadhara DJ, Bonniwell EM, et al. (January 2023). "Pharmacological Mechanism of the Non-hallucinogenic 5-HT2A Agonist Ariadne and Analogs". ACS Chemical Neuroscience. 14 (1): 119–135. doi:10.1021/acschemneuro.2c00597. PMC 10147382. PMID 36521179.
- ^ Hoyer D (November 2020). "Targeting the 5-HT system: Potential side effects". Neuropharmacology. 179: 108233. doi:10.1016/j.neuropharm.2020.108233. PMID 32805212.
- ^ 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. doi:10.1371/journal.pone.0078515. PMC 3820707. PMID 24244317.
- ^ 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.
- ^ 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.
- ^ a b c d e f g 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.
- ^ 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.
- ^ 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.
- ^ a b c d e f g h i j 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.
- ^ Nistala P (2018). "5-HT2B Receptor-mediated Cardiac Valvulopathy". VCU Theses and Dissertations. doi:10.25772/0YNR-6690.
- ^ 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.
- ^ a b 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.
- ^ 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.
- ^ a b "PDSP Ki database, University of North Carolina at Chapel Hill". Retrieved 2019-09-04.
- ^ a b c d 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.
- ^ 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.
- ^ a b 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.
- ^ 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.
- ^ a b c d e f g h i j k l m 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.
- ^ 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.
- ^ 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.
- ^ "AL-34662". Inxight Drugs. Retrieved 25 November 2024.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ a b c d e f g h i j k l m n o 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.
- ^ 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.
- ^ a b c d e f g 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.
- ^ a b 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.
- ^ 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.
- ^ 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.
- ^ a b 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.
- ^ a b c 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.
- ^ 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.
- ^ 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.
- ^ 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. doi:10.1021/acs.jmedchem.4c02174. PMID 39589936.
- ^ 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.
- ^ 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.
- ^ Name D (17 April 2024). "RQ 00310941". AdisInsight. Retrieved 30 November 2024.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ a b c 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.
- ^ a b 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.
- ^ 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.
- ^ 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.
- ^ 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.
{{cite journal}}: CS1 maint: PMC embargo expired (link) - ^ 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.
- ^ "Delving into the Latest Updates on AMAP-102 with Synapse". Synapse. 21 November 2024. Retrieved 30 November 2024.
- ^ 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.
- ^ 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.
- ^ a b 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.
- ^ 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.
- ^ "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.
- ^ 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.
- ^ 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.
- ^ "Metadoxine extended release (MDX) for adult ADHD". Alcobra Ltd. 2014. Archived from the original on 2019-02-13. Retrieved 2014-05-07.
- ^ 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.
- ^ 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.
- ^ "promethazine | Activity data visualisation tool | IUPHAR/BPS Guide to PHARMACOLOGY". www.guidetopharmacology.org. Retrieved 2019-02-28.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ "Delving into the Latest Updates on AM-1030 with Synapse". Synapse. 21 November 2024. Retrieved 30 November 2024.
- ^ 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.
- ^ 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.
- ^ a b 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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
[edit]- 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
[edit]- "5-HT2B". 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.