{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T11:08:09Z","timestamp":1794049689923,"version":"4.8.0"},"reference-count":115,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008294","name":"Louisiana State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008294","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pharmrev.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Reviews"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1016\/j.pharmr.2025.100059","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T11:55:53Z","timestamp":1745409353000},"page":"100059","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":86,"title":["5-HT2A receptors: Pharmacology and functional selectivity"],"prefix":"10.1016","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7789-1619","authenticated-orcid":false,"given":"Benjamin R.","family":"Cummins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6190-325X","authenticated-orcid":false,"given":"Gerald B.","family":"Billac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0615-0646","authenticated-orcid":false,"given":"Charles D.","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.pharmr.2025.100059_bib1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/BF00504378","article-title":"Ca2+ as messenger of 5HT2-receptor stimulation in human blood platelets","volume":"325","author":"Affolter","year":"1984","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib2","doi-asserted-by":"crossref","first-page":"14672","DOI":"10.1074\/jbc.271.25.14672","article-title":"Mapping the binding site pocket of the serotonin 5-hydroxytryptamine2A receptor. Ser3.36(159) provides a second interaction site for the protonated amine of serotonin but not of lysergic acid diethylamide or bufotenin","volume":"271","author":"Almaula","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/j.pharmr.2025.100059_bib3","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1080\/15592294.2021.2005277","article-title":"Genetic and epigenetic analysis of the serotonin 2A receptor in the context of cocaine abuse","volume":"17","author":"Alrfooh","year":"2022","journal-title":"Epigenetics"},{"key":"10.1016\/j.pharmr.2025.100059_bib4","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0026-895X(25)10753-0","article-title":"Serotonin and lysergic acid diethylamide binding in rat brain membranes: relationship to postsynaptic serotonin receptors","volume":"12","author":"Bennett","year":"1976","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib5","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/S0026-895X(25)10196-X","article-title":"5-Hydroxytryptamine type 2A receptors regulate cyclic AMP accumulation in a neuronal cell line by protein kinase C-dependent and calcium\/calmodulin-dependent mechanisms","volume":"45","author":"Berg","year":"1994","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib6","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1124\/mol.54.1.94","article-title":"Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus","volume":"54","author":"Berg","year":"1998","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib7","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nature11691","article-title":"Automated design of ligands to polypharmacological profiles","volume":"492","author":"Besnard","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.pharmr.2025.100059_bib8","doi-asserted-by":"crossref","first-page":"8269","DOI":"10.1074\/jbc.M006968200","article-title":"The dynamin-dependent, arrestin-independent internalization of 5-hydroxytryptamine 2a (5-HT2A) serotonin receptors reveals differential sorting of arrestins and 5-HT2A receptors during endocytosis","volume":"276","author":"Bhatnagar","year":"2001","journal-title":"J. Biol Chem"},{"key":"10.1016\/j.pharmr.2025.100059_bib9","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1124\/mol.106.028720","article-title":"Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists","volume":"70","author":"Braden","year":"2006","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib10","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/0028-3908(86)90207-8","article-title":"Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine","volume":"25","author":"Bradley","year":"1986","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.pharmr.2025.100059_bib11","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/S0026-895X(25)09519-7","article-title":"[3H]-DOB(4-bromo-2,5-dimethoxyphenylisopropylamine) and [3H] ketanserin label two affinity states of the cloned human 5-hydroxytryptamine2 receptor","volume":"38","author":"Branchek","year":"1990","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib12","series-title":"Progress in Brain Research","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0079-6123(08)00916-3","article-title":"Prospects for serotonin 5-HT2R pharmacotherapy in psychostimulant abuse","author":"Bubar","year":"2008"},{"key":"10.1016\/j.pharmr.2025.100059_bib113","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1124\/jpet.113.208637","article-title":"Molecular pharmacology and ligand docking studies reveal a single amino acid difference between mouse and human serotonin 5-HT2A receptors that impacts behavioral translation of novel 4-phenyl-2-dimethylaminotetralin ligands","volume":"347","author":"Canal","year":"2013","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.pharmr.2025.100059_bib13","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1126\/science.abl8615","article-title":"Structure-based discovery of nonhallucinogenic psychedelic analogs","volume":"375","author":"Cao","year":"2022","journal-title":"Science"},{"key":"10.1016\/j.pharmr.2025.100059_bib14","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S2215-0366(16)30065-7","article-title":"Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study","volume":"3","author":"Carhart-Harris","year":"2016","journal-title":"Lancet Psychiatry"},{"key":"10.1016\/j.pharmr.2025.100059_bib15","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.psyneuen.2016.11.015","article-title":"Serotonin 2A receptor (5-HT2A) gene promoter variant interacts with chronic perceived stress to modulate resting parasympathetic activity in humans","volume":"76","author":"Chang","year":"2017","journal-title":"Psychoneuroendocrinology"},{"key":"10.1016\/j.pharmr.2025.100059_bib16","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/S0026-895X(25)08564-5","article-title":"Differential ergoline and ergopeptine binding to 5-hydroxytryptamine2A receptors: ergolines require an aromatic residue at position 340 for high affinity binding","volume":"47","author":"Choudhary","year":"1995","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib17","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/0028-3908(84)90017-0","article-title":"Selective 5ht-2 antagonists inhibit serotonin stimulated phosphatidylinositol metabolism in cerebral cortex","volume":"23","author":"Conn","year":"1984","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.pharmr.2025.100059_bib18","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/0006-2952(84)90330-7","article-title":"Identification of a serotonin type 2 receptor linked to prostacyclin synthesis in vascular smooth muscle cells","volume":"33","author":"Coughlin","year":"1984","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib19","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1021\/acschemneuro.2c00170","article-title":"Tolerance and cross-tolerance among psychedelic and nonpsychedelic 5-HT2A receptor agonists in mice","volume":"13","author":"de la Fuente Revenga","year":"2022","journal-title":"ACS Chem Neurosci"},{"key":"10.1016\/j.pharmr.2025.100059_bib20","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1093\/gbe\/evu038","article-title":"The evolution of the GPCR signaling system in eukaryotes: modularity, conservation, and the transition to metazoan multicellularity","volume":"6","author":"de Mendoza","year":"2014","journal-title":"Genome Biol Evol"},{"key":"10.1016\/j.pharmr.2025.100059_bib21","first-page":"357","article-title":"Ricerche sul secreto delle cellule enterocromaffini","volume":"51","author":"Erspamer","year":"1937","journal-title":"Boll d Soc Med-Chir Pavia"},{"key":"10.1016\/j.pharmr.2025.100059_bib22","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1073\/pnas.87.6.2187","article-title":"Serotonin stimulates phospholipase A2 and the release of arachidonic acid in hippocampal neurons by a type 2 serotonin receptor that is independent of inositolphospholipid hydrolysis","volume":"87","author":"Felder","year":"1990","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.pharmr.2025.100059_bib23","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1021\/acsptsci.0c00063","article-title":"Structure\u2013activity relationship analysis of psychedelics in a rat model of asthma reveals the anti-inflammatory pharmacophore","volume":"4","author":"Flanagan","year":"2020","journal-title":"ACS Pharmacol Transl Sci"},{"key":"10.1016\/j.pharmr.2025.100059_bib24","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1021\/acsptsci.3c00297","article-title":"Serotonin-2 receptor agonists produce anti-inflammatory effects through functionally selective mechanisms that involve the suppression of disease-induced arginase 1 expression","volume":"7","author":"Flanagan","year":"2024","journal-title":"ACS Pharmacol Transl Sci"},{"key":"10.1016\/j.pharmr.2025.100059_bib25","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1080\/09540261.2018.1481827","article-title":"Psychedelics as anti-inflammatory agents","volume":"30","author":"Flanagan","year":"2018","journal-title":"Int Rev Psychiatry"},{"key":"10.1016\/j.pharmr.2025.100059_bib26","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1080\/09540261.2018.1481827","article-title":"Psychedelics as anti-inflammatory agents","volume":"30","author":"Flanagan","year":"2018","journal-title":"Int Rev Psychiatry"},{"key":"10.1016\/j.pharmr.2025.100059_bib27","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-49987-0","article-title":"Activation of 5-HT2 receptors reduces inflammation in vascular tissue and cholesterol levels in high-fat diet-fed apolipoprotein E knockout mice","volume":"9","author":"Flanagan","year":"2019","journal-title":"Sci Rep"},{"key":"10.1016\/j.pharmr.2025.100059_bib28","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nature14663","article-title":"Universal allosteric mechanism for G\u03b1 activation by GPCRs","volume":"524","author":"Flock","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.pharmr.2025.100059_bib29","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1007\/s12035-017-0457-y","article-title":"Differences in 5-HT2A and mGlu2 receptor expression levels and repressive epigenetic modifications at the 5-HT2A promoter region in the roman low- (RLA-I) and high- (RHA-I) avoidance rat strains","volume":"55","author":"Fomsgaard","year":"2018","journal-title":"Mol Neurobiol"},{"key":"10.1016\/j.pharmr.2025.100059_bib30","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1476-5381.1957.tb00142.x","article-title":"Two kinds of tryptamine receptor","volume":"12","author":"Gaddum","year":"1957","journal-title":"Br J Pharmacol Chemother"},{"key":"10.1016\/j.pharmr.2025.100059_bib31","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1016\/j.neuropharm.2007.03.013","article-title":"Role of Gq protein in behavioral effects of the hallucinogenic drug 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane","volume":"52","author":"Garcia","year":"2007","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.pharmr.2025.100059_bib32","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/j.euroneuro.2019.10.013","article-title":"Serotonin 5-HT2A receptor expression and functionality in postmortem frontal cortex of subjects with schizophrenia: selective biased agonism via G\u03b1i1-proteins","volume":"29","author":"Garc\u00eda-Bea","year":"2019","journal-title":"Eur Neuropsychopharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib33","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0026-895X(25)10241-1","article-title":"5-Hydroxytryptamine2A receptors expressed in rat renal mesangial cells inhibit cyclic AMP accumulation","volume":"48","author":"Garnovskaya","year":"1995","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib34","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.neuron.2007.01.008","article-title":"Hallucinogens recruit specific cortical 5-HT2A receptor-mediated signaling pathways to affect behavior","volume":"53","author":"Gonz\u00e1lez-Maeso","year":"2007","journal-title":"Neuron"},{"key":"10.1016\/j.pharmr.2025.100059_bib35","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/(SICI)1097-4652(199806)175:3<341::AID-JCP12>3.0.CO;2-8","article-title":"Signaling pathways mediating induction of the early response genes prostaglandin G\/H synthase-2 and egr-1 by serotonin via 5-HT2A receptors","volume":"175","author":"Goppelt-Struebe","year":"1998","journal-title":"J Cell Physiol"},{"key":"10.1016\/j.pharmr.2025.100059_bib37","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1177\/0269881116675513","article-title":"Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial","volume":"30","author":"Griffiths","year":"2016","journal-title":"J Psychopharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2020.e05809","article-title":"Aberrant alternative splicing of HTR2A exon II in peripheral blood lymphocytes of drug-na\u00efve schizophrenic patients","volume":"6","author":"Grunina","year":"2020","journal-title":"Heliyon"},{"key":"10.1016\/j.pharmr.2025.100059_bib39","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/4290430","article-title":"Serotonin-related gene variants in patients with irritable bowel syndrome and depressive or anxiety disorders","volume":"2017","author":"Grzesiak","year":"2017","journal-title":"Gastroenterol Res Pract"},{"key":"10.1016\/j.pharmr.2025.100059_bib40","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1042\/bj1480197","article-title":"The stimulation by transmitter substances and putative transmitter substances of the net activity of phospholipase A2 of synaptic membranes of cortex of guinea-pig brain","volume":"148","author":"Gullis","year":"1975","journal-title":"Biochem J"},{"key":"10.1016\/j.pharmr.2025.100059_bib41","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1006\/exnr.1993.1054","article-title":"Prenatal expression of 5-HT1C and 5-HT2 receptors in the rat central nervous system","volume":"120","author":"Hellendall","year":"1993","journal-title":"Exp Neurol"},{"key":"10.1016\/j.pharmr.2025.100059_bib42","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/j.1471-4159.1970.tb02222.x","article-title":"Effects of dopamine, gamma-aminobutyric acid and 5-hydroxytryptamine on incorporation of 32P into phosphatides in slices from the guinea pig brain","volume":"17","author":"Hokin","year":"1970","journal-title":"J Neurochem"},{"key":"10.1016\/j.pharmr.2025.100059_bib43","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1021\/acschemneuro.5b00033","article-title":"Epigenetic mechanisms of serotonin signaling","volume":"6","author":"Holloway","year":"2015","journal-title":"ACS Chem Neurosci"},{"key":"10.1016\/j.pharmr.2025.100059_bib44","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1124\/pr.114.009514","article-title":"Serotonin 5-HT 2 receptor interactions with dopamine function: implications for therapeutics in cocaine use disorder","volume":"67","author":"Howell","year":"2015","journal-title":"Pharmacol Rev"},{"key":"10.1016\/j.pharmr.2025.100059_bib45","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0006-8993(86)90903-0","article-title":"Serotonin receptors in the human brain. II. Characterization and autoradiographic localization of 5-HT1C and 5-HT2 recognition sites","volume":"376","author":"Hoyer","year":"1986","journal-title":"Brain Res"},{"key":"10.1016\/j.pharmr.2025.100059_bib46","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cellsig.2005.08.004","article-title":"Cell signalling diversity of the Gq\u03b1 family of heterotrimeric G proteins","volume":"18","author":"Hubbard","year":"2006","journal-title":"Cell Signal"},{"key":"10.1016\/j.pharmr.2025.100059_bib47","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0181865","article-title":"Anatomy and behavioral function of serotonin receptors in Drosophila melanogaster larvae","volume":"12","author":"Huser","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmr.2025.100059_bib114","doi-asserted-by":"crossref","first-page":"19575","DOI":"10.1073\/pnas.0905884106","article-title":"Rapid modulation of spine morphology by the 5-HT2A serotonin receptor through kalirin-7 signaling","volume":"106","author":"Jones","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.pharmr.2025.100059_bib48","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1126\/science.3399891","article-title":"Molecular characterization of a functional cDNA encoding the serotonin 1c receptor","volume":"241","author":"Julius","year":"1988","journal-title":"Science"},{"key":"10.1016\/j.pharmr.2025.100059_bib49","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/s41586-022-05258-z","article-title":"Bespoke library docking for 5-HT2A receptor agonists with antidepressant activity","volume":"610","author":"Kaplan","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.pharmr.2025.100059_bib50","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/s41586-019-1337-6","article-title":"Conformational transitions of a neurotensin receptor 1\u2013Gi1 complex","volume":"572","author":"Kato","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.pharmr.2025.100059_bib51","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev-pharmtox-032112-135923","article-title":"Structure-function of the G protein-coupled receptor superfamily","volume":"53","author":"Katritch","year":"2013","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"10.1016\/j.pharmr.2025.100059_bib52","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1016\/j.cell.2020.08.024","article-title":"Structure of a hallucinogen-activated Gq-coupled 5-HT(2A) serotonin receptor","volume":"182","author":"Kim","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.pharmr.2025.100059_bib53","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/s41594-018-0180-z","article-title":"Structures of the 5-HT2A receptor in complex with the antipsychotics risperidone and zotepine","volume":"26","author":"Kimura","year":"2019","journal-title":"Nat Struct Mol Biol"},{"key":"10.1016\/j.pharmr.2025.100059_bib54","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1111\/bph.15811","article-title":"Community guidelines for GPCR ligand bias: IUPHAR review 32","volume":"179","author":"Kolb","year":"2022","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib55","doi-asserted-by":"crossref","first-page":"4307","DOI":"10.1038\/s41467-024-48196-2","article-title":"G protein-specific mechanisms in the serotonin 5-HT2A receptor regulate psychosis-related effects and memory deficits","volume":"15","author":"Kossatz","year":"2024","journal-title":"Nat Commun"},{"key":"10.1016\/j.pharmr.2025.100059_bib56","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/jnc.15509","article-title":"From psychiatry to neurology: psychedelics as prospective therapeutics for neurodegenerative disorders","volume":"162","author":"Kozlowska","year":"2022","journal-title":"J Neurochem"},{"key":"10.1016\/j.pharmr.2025.100059_bib57","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.cell.2018.11.040","article-title":"Structure of a signaling cannabinoid receptor 1-G protein complex","volume":"176","author":"Krishna Kumar","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.pharmr.2025.100059_bib58","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2174\/1567205020666230825124922","article-title":"A new hope in Alzheimer\u2019s disease psychosis: pimavanserin","volume":"20","author":"Kurhan","year":"2023","journal-title":"Curr Alzheimer Res"},{"key":"10.1016\/j.pharmr.2025.100059_bib59","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1124\/jpet.102.042184","article-title":"Serotonin 5-hydroxytryptamine 2A receptor-coupled phospholipase C and phospholipase A 2 signaling pathways have different receptor reserves","volume":"304","author":"Kurrasch-Orbaugh","year":"2003","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.pharmr.2025.100059_bib60","article-title":"Sarpogrelate hydrochloride ameliorates diabetic nephropathy associated with inhibition of macrophage activity and inflammatory reaction in db\/db mice","volume":"12","author":"Lee","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmr.2025.100059_bib61","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/0024-3205(96)00423-7","article-title":"Receptor subtype and density determine the coupling repertoire of the 5-HT2 receptor subfamily","volume":"59","author":"Lucaites","year":"1996","journal-title":"Life Sci"},{"key":"10.1016\/j.pharmr.2025.100059_bib62","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1093\/protein\/7.12.1441","article-title":"Ligand-induced domain motion in the activation mechanism of a G-protein-coupled receptor","volume":"7","author":"Luo","year":"1994","journal-title":"Protein Eng"},{"key":"10.1016\/j.pharmr.2025.100059_bib116","doi-asserted-by":"crossref","first-page":"3170","DOI":"10.1016\/j.celrep.2018.05.022","article-title":"Psychedelics promote structural and functional neural plasticity","volume":"23","author":"Ly","year":"2018","journal-title":"Cell Rep"},{"key":"10.1016\/j.pharmr.2025.100059_bib63","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1126\/science.aaw5188","article-title":"Structures of the M1 and M2 muscarinic acetylcholine receptor\/G-protein complexes","volume":"364","author":"Maeda","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.pharmr.2025.100059_bib64","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.pharmthera.2015.01.009","article-title":"Structure and function of serotonin G protein-coupled receptors","volume":"150","author":"McCorvy","year":"2015","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.pharmr.2025.100059_bib65","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41594-018-0116-7","article-title":"Structural determinants of 5-HT2B receptor activation and biased agonism","volume":"25","author":"McCorvy","year":"2018","journal-title":"Nat Struct Mol Biol"},{"key":"10.1016\/j.pharmr.2025.100059_bib66","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1021\/jm060272y","article-title":"C-(4,5,6-Trimethoxyindan-1-yl)methanamine: a mescaline analogue designed using a homology model of the 5-HT2A receptor","volume":"49","author":"McLean","year":"2006","journal-title":"J Med Chem"},{"key":"10.1016\/j.pharmr.2025.100059_bib67","doi-asserted-by":"crossref","first-page":"7781","DOI":"10.1523\/JNEUROSCI.21-19-07781.2001","article-title":"Differential regulation of the mesoaccumbens circuit by serotonin 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors","volume":"21","author":"McMahon","year":"2001","journal-title":"J Neurosci"},{"key":"10.1016\/j.pharmr.2025.100059_bib68","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/npp.2009.176","article-title":"Pimavanserin, a serotonin2A receptor inverse agonist, for the treatment of Parkinson\u2019s disease psychosis","volume":"35","author":"Meltzer","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.pharmr.2025.100059_bib69","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1517\/13543784.2013.769957","article-title":"5-Hydroxytryptamine 2A receptor antagonists as potential treatment for psychiatric disorders","volume":"22","author":"Mestre","year":"2013","journal-title":"Expert Opin Investig Drugs"},{"key":"10.1016\/j.pharmr.2025.100059_bib115","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.neuropharm.2017.01.034","article-title":"Receptor-stimulated transamidation induces activation of Rac1 and Cdc42 and the regulation of dendritic spines","volume":"117","author":"Mi","year":"2017","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.pharmr.2025.100059_bib70","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.phrs.2018.09.014","article-title":"Evolutionary considerations on 5-HT2 receptors","volume":"140","author":"Moutkine","year":"2019","journal-title":"Pharmacol Res"},{"key":"10.1016\/j.pharmr.2025.100059_bib71","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.euroneuro.2020.05.004","article-title":"Pimavanserin exhibits serotonin 5-HT2A receptor inverse agonism for G\u03b1i1- and neutral antagonism for G\u03b1q\/11-proteins in human brain cortex","volume":"36","author":"Muneta-Arrate","year":"2020","journal-title":"Eur Neuropsychopharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib120","first-page":"1","article-title":"Ligand bias and inverse agonism on 5-HT2A receptor-mediated modulation of G protein activity in post-mortem human brain","author":"Muneta-Arrate","year":"2024","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib72","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1038\/s41380-018-0069-6","article-title":"5-HT2A receptor-dependent phosphorylation of mGlu2 receptor at Serine 843 promotes mGlu2 receptor-operated Gi\/o signaling","volume":"24","author":"Murat","year":"2019","journal-title":"Mol Psychiatry"},{"key":"10.1016\/j.pharmr.2025.100059_bib73","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.biopsych.2005.12.018","article-title":"Polymorphisms in the regulatory region of the human serotonin 5-HT2A receptor gene (HTR2A) influence gene expression","volume":"61","author":"Myers","year":"2007","journal-title":"Biol Psychiatry"},{"key":"10.1016\/j.pharmr.2025.100059_bib74","doi-asserted-by":"crossref","first-page":"L191","DOI":"10.1152\/ajplung.00138.2013","article-title":"Serotonin 5-HT 2 receptor activation prevents allergic asthma in a mouse model","volume":"308","author":"Nau","year":"2015","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.pharmr.2025.100059_bib75","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0075426","article-title":"Serotonin 5-HT2A receptor activation blocks TNF-\u03b1 mediated inflammation in vivo","volume":"8","author":"Nau","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmr.2025.100059_bib76","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.pharmthera.2003.11.002","article-title":"Hallucinogens","volume":"101","author":"Nichols","year":"2004","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.pharmr.2025.100059_bib77","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1124\/pr.115.011478","article-title":"Psychedelics","volume":"68","author":"Nichols","year":"2016","journal-title":"Pharmacol Rev"},{"key":"10.1016\/j.pharmr.2025.100059_bib78","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1021\/cr078224o","article-title":"Serotonin receptors","volume":"108","author":"Nichols","year":"2008","journal-title":"Chem Rev"},{"key":"10.1016\/j.pharmr.2025.100059_bib79","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1472-6807-13-3","article-title":"The role of cysteine 6.47 in class A GPCRs","volume":"13","author":"Olivella","year":"2013","journal-title":"BMC Struct Biol"},{"key":"10.1016\/j.pharmr.2025.100059_bib80","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1017\/S0033291718001356","article-title":"Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial","volume":"49","author":"Palhano-Fontes","year":"2019","journal-title":"Psychol Med"},{"key":"10.1016\/j.pharmr.2025.100059_bib81","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/0014-2999(84)90057-8","article-title":"The binding of serotonergic ligands to the porcine choroid plexus: characterization of a new type of serotonin recognition site","volume":"106","author":"Pazos","year":"1984","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib82","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.cell.2018.01.001","article-title":"5-HT2C receptor structures reveal the structural basis of GPCR polypharmacology","volume":"172","author":"Peng","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.pharmr.2025.100059_bib83","doi-asserted-by":"crossref","first-page":"16044","DOI":"10.1021\/ja508394x","article-title":"A functional selectivity mechanism at the serotonin-2A GPCR involves ligand-dependent conformations of intracellular loop 2","volume":"136","author":"Perez-Aguilar","year":"2014","journal-title":"J Am Chem Soc"},{"key":"10.1016\/j.pharmr.2025.100059_bib84","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/S0026-895X(25)13813-3","article-title":"Serotonin receptor binding sites affected differentially by guanine nucleotides","volume":"16","author":"Peroutka","year":"1979","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib118","doi-asserted-by":"crossref","first-page":"12031","DOI":"10.1021\/acs.jmedchem.2c00702","article-title":"Discovery of \u03b2-arrestin-biased 25CN-NBOH-derived 5-HT2A receptor agonists","volume":"65","author":"Poulie","year":"2022","journal-title":"J Med Chem"},{"key":"10.1016\/j.pharmr.2025.100059_bib86","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.35082","article-title":"Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor","volume":"7","author":"Preller","year":"2018","journal-title":"eLife"},{"key":"10.1016\/j.pharmr.2025.100059_bib87","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0091-3057(01)00720-1","article-title":"5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens","volume":"72","author":"Rabin","year":"2002","journal-title":"Pharmacol Biochem Behav"},{"key":"10.1016\/j.pharmr.2025.100059_bib88","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/S0021-9258(18)57137-4","article-title":"Serum vasoconstrictor, serotonin; isolation and characterization","volume":"176","author":"Rapport","year":"1948","journal-title":"J Biol Chem"},{"key":"10.1016\/j.pharmr.2025.100059_bib89","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-96736-3","article-title":"LSD-stimulated behaviors in mice require \u03b2-arrestin 2 but not \u03b2-arrestin 1","volume":"11","author":"Rodriguiz","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.pharmr.2025.100059_bib90","doi-asserted-by":"crossref","first-page":"208","DOI":"10.4238\/vol9-1gmr718","article-title":"Association between the -1438A\/G polymorphism of the serotonin 2A receptor gene and late-onset psoriasis in a Thai population","volume":"9","author":"Ronpirin","year":"2010","journal-title":"Genet Mol Res"},{"key":"10.1016\/j.pharmr.2025.100059_bib91","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/0028-3908(84)90244-2","article-title":"Aortic recognition sites for serotonin (5HT) are coupled to phospholipase C and modulate phosphatidylinositol turnover","volume":"23","author":"Roth","year":"1984","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.pharmr.2025.100059_bib92","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12863-015-0325-6","article-title":"Genomic structure and expression of the human serotonin 2A receptor gene (HTR2A) locus: identification of novel HTR2A and antisense (HTR2A-AS1) exons","volume":"17","author":"Ruble","year":"2016","journal-title":"BMC Genet"},{"key":"10.1016\/j.pharmr.2025.100059_bib93","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2023.1239159","article-title":"\u03bc-opioid receptor agonists and psychedelics: pharmacological opportunities and challenges","volume":"14","author":"Salinsky","year":"2023","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib94","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1046\/j.1471-4159.1997.68051998.x","article-title":"Identification of an endogenous 5-hydroxytryptamine2A receptor in NIH-3T3 cells: agonist-induced down-regulation involves decreases in receptor RNA and number","volume":"68","author":"Saucier","year":"1997","journal-title":"J Neurochem"},{"key":"10.1016\/j.pharmr.2025.100059_bib95","doi-asserted-by":"crossref","first-page":"13513","DOI":"10.1523\/JNEUROSCI.1665-10.2010","article-title":"Serotonin, but not N-methyltryptamines, activates the serotonin 2A receptor via a \u03b2-arrestin2\/Src\/Akt signaling complex in vivo","volume":"30","author":"Schmid","year":"2010","journal-title":"J Neurosci"},{"key":"10.1016\/j.pharmr.2025.100059_bib96","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1073\/pnas.0708862105","article-title":"Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo","volume":"105","author":"Schmid","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.pharmr.2025.100059_bib97","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1038\/npp.2014.38","article-title":"Clozapine acts as an agonist at serotonin 2A receptors to counter MK-801-induced behaviors through a \u03b2arrestin2-independent activation of Akt","volume":"39","author":"Schmid","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.pharmr.2025.100059_bib119","doi-asserted-by":"crossref","unstructured":"Schmitz GP, Chiu YT, K\u00f6nig GM, Kostenis E, Roth BL, Herman MA. Psychedelic compounds directly excite 5-HT2A Layer 5 Pyramidal Neurons in the Prefrontal Cortex through a 5-HT2A Gq -mediated activation mechanism. Preprint. Posted online November 15, 2022. bioRxiv 2022.11.15.516655. https:\/\/doi.org\/10.1101\/2022.11.15.516655","DOI":"10.1101\/2022.11.15.516655"},{"key":"10.1016\/j.pharmr.2025.100059_bib98","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/apha.12430","article-title":"The role of serotonin and its receptors in activation of immune responses and inflammation","volume":"213","author":"Shajib","year":"2015","journal-title":"Acta Physiol"},{"key":"10.1016\/j.pharmr.2025.100059_bib99","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/jnc.15540","article-title":"Molecular insights into psychedelic drug action","volume":"162","author":"Slocum","year":"2022","journal-title":"J Neurochem"},{"key":"10.1016\/j.pharmr.2025.100059_bib100","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1152\/ajplegacy.1953.175.1.157","article-title":"Serotonin content of some mammalian tissues and urine and a method for its determination","volume":"175","author":"Twarog","year":"1953","journal-title":"Am J Physiol"},{"key":"10.1016\/j.pharmr.2025.100059_bib101","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/jpet.106.104463","article-title":"Functional selectivity and classical concepts of quantitative pharmacology","volume":"320","author":"Urban","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.pharmr.2025.100059_bib102","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1126\/science.1232808","article-title":"Structural features for functional selectivity at serotonin receptors","volume":"340","author":"Wacker","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.pharmr.2025.100059_bib103","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.cell.2016.12.033","article-title":"Crystal structure of an LSD-bound human serotonin receptor","volume":"168","author":"Wacker","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.pharmr.2025.100059_bib104","doi-asserted-by":"crossref","first-page":"8221","DOI":"10.1038\/s41467-023-44016-1","article-title":"Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential","volume":"14","author":"Wallach","year":"2023","journal-title":"Nat Commun"},{"key":"10.1016\/j.pharmr.2025.100059_bib105","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1126\/science.1232807","article-title":"Structural basis for molecular recognition at serotonin receptors","volume":"340","author":"Wang","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.pharmr.2025.100059_bib106","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.phrs.2018.06.015","article-title":"Beyond a neurotransmitter: the role of serotonin in inflammation and immunity","volume":"140","author":"Wu","year":"2019","journal-title":"Pharmacol Res"},{"key":"10.1016\/j.pharmr.2025.100059_bib107","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1007\/s12110-016-9257-8","article-title":"Gender interacts with opioid receptor polymorphism A118G and serotonin receptor polymorphism \u22121438 A\/G on speed-dating success","volume":"27","author":"Wu","year":"2016","journal-title":"Hum Nat"},{"key":"10.1016\/j.pharmr.2025.100059_bib109","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1021\/jm00059a021","article-title":"Signal transduction by a 5-HT2 receptor: A mechanistic hypothesis from molecular dynamics simulations of the three-dimensional model of the receptor complexed to ligands","volume":"36","author":"Zhang","year":"1993","journal-title":"J Med Chem"},{"key":"10.1016\/j.pharmr.2025.100059_bib110","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3389\/fphar.2015.00225","article-title":"The role of serotonin 5-HT2A receptors in memory and cognition","volume":"6","author":"Zhang","year":"2015","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.pharmr.2025.100059_bib112","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2023.176038","article-title":"G\u03b2\u03b3 subunit inhibitor decreases DOM-induced head twitch response via the PLC\u03b2\/IP3\/Ca2+\/ERK and cAMP signaling pathways","volume":"957","author":"Zhu","year":"2023","journal-title":"Eur J Pharmacol"}],"container-title":["Pharmacological Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0031699725074678?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0031699725074678?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:57:45Z","timestamp":1759964265000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0031699725074678"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":115,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["S0031699725074678"],"URL":"https:\/\/doi.org\/10.1016\/j.pharmr.2025.100059","relation":{},"ISSN":["0031-6997"],"issn-type":[{"value":"0031-6997","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"5-HT2A receptors: Pharmacology and functional selectivity","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Reviews","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pharmr.2025.100059","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc. on behalf of American Society for Pharmacology and Experimental Therapeutics.","name":"copyright","label":"Copyright"}],"article-number":"100059"}}