{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:17:36Z","timestamp":1790399856900,"version":"4.1.0"},"reference-count":88,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["P5R5PM_206796"],"award-info":[{"award-number":["P5R5PM_206796"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["TMSGI3_211261"],"award-info":[{"award-number":["TMSGI3_211261"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004385","name":"Universiteit Gent","doi-asserted-by":"publisher","award":["BOF23\/PDO\/073"],"award-info":[{"award-number":["BOF23\/PDO\/073"]}],"id":[{"id":"10.13039\/501100004385","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA000522\u201316"],"award-info":[{"award-number":["DA000522\u201316"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Various ring-substituted \u03b1-methylphenethylamines (i.e., amphetamines) produce psychedelic-like effects that are primarily mediated by activity at 5-hydroxytryptamine 2A (5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    ) receptors. Small lipophilic substituents at the 4-position of the 2,5-dimethoxyamphetamine core structure can greatly enhance the clinical potency of such derivatives. Here, we studied the effects of various 4-alkylated 2,5-dimethoxyamphetamines (4-methyl, 4-ethyl, 4-propyl, 4-butyl, 4-amyl) on in vitro receptor activities and in vivo psychedelic-like effects in mice. The acute effects of the compounds were examined using the mouse head-twitch response (HTR) assay, a proxy for psychedelic-like drug actions. Overall, the series primarily interacted with 5-HT\n                    <jats:sub>2<\/jats:sub>\n                    receptor subtypes, with increasing 4-alkyl chain length associated with increased affinity at 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    receptors. For all three in vitro functional readouts assessed, the 4-propyl analog produced the highest potencies for 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    receptor activation (1\u20139\u2009nM), but smaller and longer chain lengths displayed comparable activities (2\u201356\u2009nM). In mice, the compounds displayed variable maximal HTR counts (23\u2013119) and potencies (0.42\u20132.76\u2009mg\/kg), with the 4-propyl and 4-methyl compounds being the most potent and efficacious, respectively. Analysis of drug concentrations in mouse plasma, brain tissue, and brain dialysate samples revealed that derivatives with longer alkyl chains (i.e., butyl, amyl) require higher systemic doses to achieve concentrations comparable to those of short-chain analogs. These findings demonstrate that extending the 4-position alkyl chain beyond a propyl group reduces in vivo potency and efficacy, in part due to pharmacokinetic parameters.\n                  <\/jats:p>","DOI":"10.1038\/s41380-025-03325-1","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T10:59:30Z","timestamp":1762340370000},"page":"1799-1809","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The 4-alkyl chain length of 2,5-dimethoxyamphetamines differentially affects in vitro serotonin receptor actions versus in vivo psychedelic-like effects"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0874-4875","authenticated-orcid":false,"given":"Dino","family":"Luethi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant C.","family":"Glatfelter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9077-4055","authenticated-orcid":false,"given":"Eline","family":"Pottie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Sellitti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander D.","family":"Maitland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas R.","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1901-6024","authenticated-orcid":false,"given":"Lindsay A.","family":"Kryszak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelley N.","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-6250","authenticated-orcid":false,"given":"Marius C.","family":"Hoener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7126-348X","authenticated-orcid":false,"given":"Christophe P.","family":"Stove","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1765-9659","authenticated-orcid":false,"given":"Matthias E.","family":"Liechti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2758-2680","authenticated-orcid":false,"given":"Martin","family":"Smie\u0161ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3512-4057","authenticated-orcid":false,"given":"Linda D.","family":"Simmler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3069-9732","authenticated-orcid":false,"given":"Deborah","family":"Rudin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"3325_CR1","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/s41593-022-01177-4","volume":"25","author":"AC Kwan","year":"2022","unstructured":"Kwan AC, Olson DE, Preller KH, Roth BL. The neural basis of psychedelic action. Nat Neurosci. 2022;25:1407\u201319.","journal-title":"Nat Neurosci"},{"key":"3325_CR2","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1124\/pr.115.011478","volume":"68","author":"DE Nichols","year":"2016","unstructured":"Nichols DE. Psychedelics. Pharmacol Rev. 2016;68:264\u2013355.","journal-title":"Pharmacol Rev"},{"key":"3325_CR3","doi-asserted-by":"crossref","first-page":"3595","DOI":"10.1038\/s41380-023-02274-x","volume":"28","author":"AM Jaster","year":"2023","unstructured":"Jaster AM, Gonz\u00e1lez-Maeso J. Mechanisms and molecular targets surrounding the potential therapeutic effects of psychedelics. Mol Psychiatry. 2023;28:3595\u2013612.","journal-title":"Mol Psychiatry"},{"key":"3325_CR4","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s00204-020-02693-7","volume":"94","author":"D Luethi","year":"2020","unstructured":"Luethi D, Liechti ME. Designer drugs: mechanism of action and adverse effects. Arch Toxicol. 2020;94:1085\u2013133.","journal-title":"Arch Toxicol"},{"key":"3325_CR5","doi-asserted-by":"crossref","DOI":"10.1016\/j.expneurol.2021.113778","volume":"343","author":"D Rudin","year":"2021","unstructured":"Rudin D, Liechti ME, Luethi D. Molecular and clinical aspects of potential neurotoxicity induced by new psychoactive stimulants and psychedelics. Exp Neurol. 2021;343:113778.","journal-title":"Exp Neurol"},{"key":"3325_CR6","doi-asserted-by":"crossref","first-page":"206","DOI":"10.3389\/fphar.2018.00206","volume":"9","author":"E Papaseit","year":"2018","unstructured":"Papaseit E, Farr\u00e9 M, P\u00e9rez-Ma\u00f1\u00e1 C, Torrens M, Ventura M, Pujadas M, et al. Acute pharmacological effects of 2C-B in humans: an observational study. Front Pharmacol. 2018;9:206.","journal-title":"Front Pharmacol"},{"key":"3325_CR7","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3389\/fphar.2020.00233","volume":"11","author":"E Papaseit","year":"2020","unstructured":"Papaseit E, Olesti E, P\u00e9rez-Ma\u00f1\u00e1 C, Torrens M, Grifell M, Ventura M, et al. Acute effects of 2C-E in humans: an observational study. Front Pharmacol. 2020;11:233.","journal-title":"Front Pharmacol"},{"key":"3325_CR8","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/7854_2016_64","volume":"32","author":"AL Halberstadt","year":"2017","unstructured":"Halberstadt AL. Pharmacology and toxicology of N-benzylphenethylamine (\u201cNBOMe\u201d) hallucinogens. Curr Top Behav Neurosci. 2017;32:283\u2013311.","journal-title":"Curr Top Behav Neurosci"},{"key":"3325_CR9","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.neuropharm.2015.08.034","volume":"99","author":"A Rickli","year":"2015","unstructured":"Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME. Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology. 2015;99:546\u201353.","journal-title":"Neuropharmacology"},{"key":"3325_CR10","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s00213-013-3303-6","volume":"231","author":"AJ Eshleman","year":"2014","unstructured":"Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB. Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function. Psychopharmacology (Berl). 2014;231:875\u201388.","journal-title":"Psychopharmacology (Berl)"},{"key":"3325_CR11","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.bcp.2018.09.024","volume":"158","author":"AJ Eshleman","year":"2018","unstructured":"Eshleman AJ, Wolfrum KM, Reed JF, Kim SO, Johnson RA, Janowsky A. Neurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: high potency agonists at 5-HT2A receptors. Biochem Pharmacol. 2018;158:27\u201334.","journal-title":"Biochem Pharmacol"},{"key":"3325_CR12","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1124\/jpet.106.117507","volume":"321","author":"PR Moya","year":"2007","unstructured":"Moya PR, Berg KA, Guti\u00e9rrez-Hernandez MA, S\u00e1ez-Briones P, Reyes-Parada M, Cassels BK, et al. Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors. J Pharmacol Exp Ther. 2007;321:1054\u201361.","journal-title":"J Pharmacol Exp Ther"},{"key":"3325_CR13","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1124\/jpet.117.239905","volume":"361","author":"AA Jensen","year":"2017","unstructured":"Jensen AA, McCorvy JD, Leth-Petersen S, Bundgaard C, Liebscher G, Kenakin TP, et al. Detailed characterization of the in vitro pharmacological and pharmacokinetic properties of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine (25CN-NBOH), a highly selective and brain-penetrant 5-HT2A receptor agonist. J Pharmacol Exp Ther. 2017;361:441\u201353.","journal-title":"J Pharmacol Exp Ther"},{"key":"3325_CR14","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.3389\/fphar.2019.01423","volume":"10","author":"KE Kolaczynska","year":"2019","unstructured":"Kolaczynska KE, Luethi D, Trachsel D, Hoener MC, Liechti ME. Receptor interaction profiles of 4-alkoxy-substituted 2,5-dimethoxyphenethylamines and related amphetamines. Front Pharmacol. 2019;10:1423.","journal-title":"Front Pharmacol"},{"key":"3325_CR15","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.neuropharm.2017.07.012","volume":"134","author":"D Luethi","year":"2018","unstructured":"Luethi D, Trachsel D, Hoener MC, Liechti ME. Monoamine receptor interaction profiles of 4-thio-substituted phenethylamines (2C-T drugs). Neuropharmacology. 2018;134:141\u20138.","journal-title":"Neuropharmacology"},{"key":"3325_CR16","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ejphar.2019.05.014","volume":"855","author":"D Luethi","year":"2019","unstructured":"Luethi D, Widmer R, Trachsel D, Hoener MC, Liechti ME. Monoamine receptor interaction profiles of 4-aryl-substituted 2,5-dimethoxyphenethylamines (2C-BI derivatives). Eur J Pharmacol. 2019;855:103\u201311.","journal-title":"Eur J Pharmacol"},{"key":"3325_CR17","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.neuropharm.2018.02.033","volume":"142","author":"JS Elmore","year":"2018","unstructured":"Elmore JS, Decker AM, Sulima A, Rice KC, Partilla JS, Blough BE, et al. Comparative neuropharmacology of N-(2-methoxybenzyl)-2,5-dimethoxyphenethylamine (NBOMe) hallucinogens and their 2C counterparts in male rats. Neuropharmacology. 2018;142:240\u201350.","journal-title":"Neuropharmacology"},{"key":"3325_CR18","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.neuropharm.2013.08.025","volume":"77","author":"AL Halberstadt","year":"2014","unstructured":"Halberstadt AL, Geyer MA. Effects of the hallucinogen 2,5-dimethoxy-4-iodophenethylamine (2C-I) and superpotent N-benzyl derivatives on the head twitch response. Neuropharmacology. 2014;77:200\u20137.","journal-title":"Neuropharmacology"},{"key":"3325_CR19","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/s00213-005-0009-4","volume":"181","author":"WE Fantegrossi","year":"2005","unstructured":"Fantegrossi WE, Harrington AW, Eckler JR, Arshad S, Rabin RA, Winter JC, et al. Hallucinogen-like actions of 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7) in mice and rats. Psychopharmacology (Berl). 2005;181:496\u2013503.","journal-title":"Psychopharmacology (Berl)"},{"key":"3325_CR20","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2019.107933","volume":"167","author":"AL Halberstadt","year":"2020","unstructured":"Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD. Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology. 2020;167:107933.","journal-title":"Neuropharmacology"},{"key":"3325_CR21","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1177\/0269881119826610","volume":"33","author":"AL Halberstadt","year":"2019","unstructured":"Halberstadt AL, Chatha M, Chapman SJ, Brandt SD. Comparison of the behavioral effects of mescaline analogs using the head twitch response in mice. J Psychopharmacol. 2019;33:406\u201314.","journal-title":"J Psychopharmacol"},{"key":"3325_CR22","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s00213-022-06279-2","volume":"240","author":"AL Halberstadt","year":"2023","unstructured":"Halberstadt AL, Luethi D, Hoener MC, Trachsel D, Brandt SD, Liechti ME. Use of the head-twitch response to investigate the structure-activity relationships of 4-thio-substituted 2,5-dimethoxyphenylalkylamines. Psychopharmacology (Berl). 2023;240:115\u201326.","journal-title":"Psychopharmacology (Berl)"},{"key":"3325_CR23","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1021\/acsptsci.1c00237","volume":"5","author":"GC Glatfelter","year":"2022","unstructured":"Glatfelter GC, Chojnacki MR, McGriff SA, Wang T, Baumann MH. Automated computer software assessment of 5-hydroxytryptamine 2A receptor-mediated head twitch responses from video recordings of mice. ACS Pharmacol Transl Sci. 2022;5:321\u201330.","journal-title":"ACS Pharmacol Transl Sci"},{"key":"3325_CR24","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1021\/acsptsci.2c00222","volume":"6","author":"GC Glatfelter","year":"2023","unstructured":"Glatfelter GC, Naeem M, Pham DNK, Golen JA, Chadeayne AR, Manke DR, et al. Receptor binding profiles for tryptamine psychedelics and effects of 4-propionoxy-N,N-dimethyltryptamine in mice. ACS Pharmacol Transl Sci. 2023;6:567\u201377.","journal-title":"ACS Pharmacol Transl Sci"},{"key":"3325_CR25","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1021\/acsptsci.3c00192","volume":"7","author":"GC Glatfelter","year":"2024","unstructured":"Glatfelter GC, Pottie E, Partilla JS, Stove CP, Baumann MH. Comparative pharmacological effects of lisuride and lysergic acid diethylamide revisited. ACS Pharmacol Transl Sci. 2024;7:641\u201353.","journal-title":"ACS Pharmacol Transl Sci"},{"key":"3325_CR26","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-44016-1","volume":"14","author":"J Wallach","year":"2023","unstructured":"Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, et al. Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential. Nat Commun. 2023;14:8221.","journal-title":"Nat Commun"},{"key":"3325_CR27","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1177\/02698811231225609","volume":"38","author":"A Rouaud","year":"2024","unstructured":"Rouaud A, Calder AE, Hasler G. Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: comparison to known cardiotoxins. J Psychopharmacol. 2024;38:217\u201324.","journal-title":"J Psychopharmacol"},{"key":"3325_CR28","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1038\/npp.2009.29","volume":"34","author":"AL Halberstadt","year":"2009","unstructured":"Halberstadt AL, van der Heijden I, Ruderman MA, Risbrough VB, Gingrich JA, Geyer MA, et al. 5-HT2A and 5-HT2C receptors exert opposing effects on locomotor activity in mice. Neuropsychopharmacology. 2009;34:1958\u201367.","journal-title":"Neuropsychopharmacology"},{"key":"3325_CR29","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1124\/jpet.110.172247","volume":"335","author":"WE Fantegrossi","year":"2010","unstructured":"Fantegrossi WE, Simoneau J, Cohen MS, Zimmerman SM, Henson CM, Rice KC, et al. Interaction of 5-HT2A and 5-HT2C receptors in R(-)-2,5-dimethoxy-4-iodoamphetamine-elicited head twitch behavior in mice. J Pharmacol Exp Ther. 2010;335:728\u201334.","journal-title":"J Pharmacol Exp Ther"},{"key":"3325_CR30","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s00213-010-1784-0","volume":"209","author":"CE Canal","year":"2010","unstructured":"Canal CE, Olaghere da Silva UB, Gresch PJ, Watt EE, Sanders-Bush E, Airey DC. The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen. Psychopharmacology (Berl). 2010;209:163\u201374.","journal-title":"Psychopharmacology (Berl)"},{"key":"3325_CR31","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1007\/s00213-023-06482-9","volume":"242","author":"RJP Custodio","year":"2025","unstructured":"Custodio RJP, Ortiz DM, Lee HJ, Sayson LV, Kim M, Lee YS, et al. Serotonin 2C receptors are also important in head-twitch responses in male mice. Psychopharmacology (Berl). 2025;242:1585\u2013605.","journal-title":"Psychopharmacology (Berl)"},{"key":"3325_CR32","doi-asserted-by":"crossref","first-page":"9856","DOI":"10.1523\/JNEUROSCI.21-24-09856.2001","volume":"21","author":"R Mart\u00edn-Ruiz","year":"2001","unstructured":"Mart\u00edn-Ruiz R, Puig MV, Celada P, Shapiro DA, Roth BL, Mengod G, et al. Control of serotonergic function in medial prefrontal cortex by serotonin-2A receptors through a glutamate-dependent mechanism. J Neurosci. 2001;21:9856\u201366.","journal-title":"J Neurosci"},{"key":"3325_CR33","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/0306-4522(91)90128-B","volume":"40","author":"R Araneda","year":"1991","unstructured":"Araneda R, Andrade R. 5-Hydroxytryptamine2 and 5-hydroxytryptamine1A receptors mediate opposing responses on membrane excitability in rat association cortex. Neuroscience. 1991;40:399\u2013412.","journal-title":"Neuroscience"},{"key":"3325_CR34","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1038\/s41380-024-02506-8","volume":"29","author":"P Puigseslloses","year":"2024","unstructured":"Puigseslloses P, Nadal-Gratac\u00f3s N, Ketsela G, Weiss N, Berzosa X, Estrada-Tejedor R, et al. Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: insights into psychoactive and thermoregulatory properties. Mol Psychiatry. 2024;29:2346\u201358.","journal-title":"Mol Psychiatry"},{"key":"3325_CR35","doi-asserted-by":"crossref","first-page":"4458","DOI":"10.1021\/acschemneuro.4c00513","volume":"15","author":"GC Glatfelter","year":"2024","unstructured":"Glatfelter GC, Clark AA, Cavalco NG, Landavazo A, Partilla JS, Naeem M, et al. Serotonin 1A receptors modulate serotonin 2A receptor-mediated behavioral effects of 5-methoxy-N,N-dimethyltryptamine analogs in mice. ACS Chem Neurosci. 2024;15:4458\u201377.","journal-title":"ACS Chem Neurosci"},{"key":"3325_CR36","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1021\/acsptsci.2c00177","volume":"5","author":"GC Glatfelter","year":"2022","unstructured":"Glatfelter GC, Pottie E, Partilla JS, Sherwood AM, Kaylo K, Pham DNK, et al. Structure-activity relationships for psilocybin, baeocystin, aeruginascin, and related analogues to produce pharmacological effects in mice. ACS Pharmacol Transl Sci. 2022;5:1181\u201396.","journal-title":"ACS Pharmacol Transl Sci"},{"key":"3325_CR37","doi-asserted-by":"crossref","first-page":"113612","DOI":"10.1016\/j.biopha.2022.113612","volume":"154","author":"I Erkizia-Santamar\u00eda","year":"2022","unstructured":"Erkizia-Santamar\u00eda I, Alles-Pascual R, Horrillo I, Meana JJ, Ortega JE. Serotonin 5-HT2A, 5-HT2C and 5-HT1A receptor involvement in the acute effects of psilocybin in mice. In vitro pharmacological profile and modulation of thermoregulation and head-twich response. Biomed Pharmacother. 2022;154:113612.","journal-title":"Biomed Pharmacother"},{"key":"3325_CR38","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/dta.2222","volume":"10","author":"SD Brandt","year":"2018","unstructured":"Brandt SD, Kavanagh PV, Twamley B, Westphal F, Elliott SP, Wallach J, et al. Return of the lysergamides. Part IV: analytical and pharmacological characterization of lysergic acid morpholide (LSM-775). Drug Test Anal. 2018;10:310\u201322.","journal-title":"Drug Test Anal"},{"key":"3325_CR39","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.euroneuro.2016.01.005","volume":"26","author":"T Pokorny","year":"2016","unstructured":"Pokorny T, Preller KH, Kraehenmann R, Vollenweider FX. Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A\/2A agonist ergotamine on psilocybin-induced psychedelic experience. Eur Neuropsychopharmacol. 2016;26:756\u201366.","journal-title":"Eur Neuropsychopharmacol"},{"key":"3325_CR40","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0166-4328(96)00081-2","volume":"73","author":"RJ Strassman","year":"1996","unstructured":"Strassman RJ. Human psychopharmacology of N,N-dimethyltryptamine. Behav Brain Res. 1996;73:121\u20134.","journal-title":"Behav Brain Res"},{"key":"3325_CR41","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/s41586-024-07403-2","volume":"630","author":"AL Warren","year":"2024","unstructured":"Warren AL, Lankri D, Cunningham MJ, Serrano IC, Parise LF, Kruegel AC, et al. Structural pharmacology and therapeutic potential of 5-methoxytryptamines. Nature. 2024;630:237\u201346.","journal-title":"Nature"},{"key":"3325_CR42","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1093\/ijnp\/pyy047","volume":"21","author":"D Luethi","year":"2018","unstructured":"Luethi D, Liechti ME. Monoamine transporter and receptor interaction profiles in vitro predict reported human doses of novel psychoactive stimulants and psychedelics. Int J Neuropsychopharmacol. 2018;21:926\u201331.","journal-title":"Int J Neuropsychopharmacol"},{"key":"3325_CR43","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1002\/dta.1333","volume":"4","author":"CE Canal","year":"2012","unstructured":"Canal CE, Morgan D. Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model. Drug Test Anal. 2012;4:556\u201376.","journal-title":"Drug Test Anal"},{"key":"3325_CR44","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/0091-3057(90)90098-3","volume":"36","author":"NA Darmani","year":"1990","unstructured":"Darmani NA, Martin BR, Pandey U, Glennon RA. Do functional relationships exist between 5-HT1A and 5-HT2 receptors? Pharmacol Biochem Behav. 1990;36:901\u20136.","journal-title":"Pharmacol Biochem Behav"},{"key":"3325_CR45","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1002\/dta.2494","volume":"11","author":"L Wagmann","year":"2019","unstructured":"Wagmann L, Brandt SD, Stratford A, Maurer HH, Meyer MR. Interactions of phenethylamine-derived psychoactive substances of the 2C-series with human monoamine oxidases. Drug Test Anal. 2019;11:318\u201324.","journal-title":"Drug Test Anal"},{"key":"3325_CR46","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.toxlet.2018.07.018","volume":"295","author":"C Noble","year":"2018","unstructured":"Noble C, Holm NB, Mardal M, Linnet K. Bromo-dragonfly, a psychoactive benzodifuran, is resistant to hepatic metabolism and potently inhibits monoamine oxidase A. Toxicol Lett. 2018;295:397\u2013407.","journal-title":"Toxicol Lett"},{"key":"3325_CR47","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1007\/s00204-023-03465-9","volume":"97","author":"MH Deventer","year":"2023","unstructured":"Deventer MH, Persson M, Laus A, Pottie E, Cannaert A, Tocco G, et al. Off-target activity of NBOMes and NBOMe analogs at the \u00b5 opioid receptor. Arch Toxicol. 2023;97:1367\u201384.","journal-title":"Arch Toxicol"},{"key":"3325_CR48","unstructured":"Shulgin A, Shulgin A PiHKAL: A Chemical Love Story. Transform Press: Berkley, 1991."},{"key":"3325_CR49","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1021\/acsptsci.3c00297","volume":"7","author":"TW Flanagan","year":"2024","unstructured":"Flanagan TW, Foster TP, Galbato TE, Lum PY, Louie B, Song G, et al. Serotonin-2 receptor agonists produce anti-inflammatory effects through functionally selective mechanisms that involve the suppression of disease-induced arginase 1 expression. ACS Pharmacol Transl Sci. 2024;7:478\u201392.","journal-title":"ACS Pharmacol Transl Sci"},{"key":"3325_CR50","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1007\/BF02147960","volume":"20","author":"AT Shulgin","year":"1964","unstructured":"Shulgin AT. Psychotomimetic amphetamines: methoxy 3,4-dialkoxyamphetamines. Experientia. 1964;20:366\u20137.","journal-title":"Experientia"},{"key":"3325_CR51","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1126\/science.158.3801.669","volume":"158","author":"SH Snyder","year":"1967","unstructured":"Snyder SH, Faillace L, Hollister L. 2,5-Dimethoxy-4-methyl-amphetamine (STP): a new hallucinogenic drug. Science. 1967;158:669\u201370.","journal-title":"Science"},{"key":"3325_CR52","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1021\/jm00246a006","volume":"18","author":"AT Shulgin","year":"1975","unstructured":"Shulgin AT, Dyer DC. Psychotomimetic phenylisopropylamines. 5. 4-Alkyl-2,5-dimethoxyphenylisopropylamines. J Med Chem. 1975;18:1201\u20134.","journal-title":"J Med Chem"},{"key":"3325_CR53","doi-asserted-by":"crossref","first-page":"8485","DOI":"10.1073\/pnas.1103029108","volume":"108","author":"FG Revel","year":"2011","unstructured":"Revel FG, Moreau JL, Gainetdinov RR, Bradaia A, Sotnikova TD, Mory R, et al. TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity. Proc Natl Acad Sci USA. 2011;108:8485\u201390.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3325_CR54","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1126\/science.abl8615","volume":"375","author":"D Cao","year":"2022","unstructured":"Cao D, Yu J, Wang H, Luo Z, Liu X, He L, et al. Structure-based discovery of nonhallucinogenic psychedelic analogs. Science. 2022;375:403\u201311.","journal-title":"Science"},{"key":"3325_CR55","doi-asserted-by":"crossref","first-page":"111211","DOI":"10.1016\/j.celrep.2022.111211","volume":"40","author":"RH Gumpper","year":"2022","unstructured":"Gumpper RH, Fay JF, Roth BL. Molecular insights into the regulation of constitutive activity by RNA editing of 5HT2C serotonin receptors. Cell Rep. 2022;40:111211.","journal-title":"Cell Rep"},{"key":"3325_CR56","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1021\/acschemneuro.2c00170","volume":"13","author":"M de la Fuente Revenga","year":"2022","unstructured":"de la Fuente Revenga M, Jaster AM, McGinn J, Silva G, Saha S, Gonz\u00e1lez-Maeso J. Tolerance and cross-tolerance among psychedelic and nonpsychedelic 5-HT2A receptor agonists in mice. ACS Chem Neurosci. 2022;13:2436\u201348.","journal-title":"ACS Chem Neurosci"},{"key":"3325_CR57","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1111\/bph.13899","volume":"174","author":"LD Simmler","year":"2017","unstructured":"Simmler LD, Anacker AMJ, Levin MH, Vaswani NM, Gresch PJ, Nackenoff AG, et al. Blockade of the 5-HT transporter contributes to the behavioural, neuronal and molecular effects of cocaine. Br J Pharmacol. 2017;174:2716\u201338.","journal-title":"Br J Pharmacol"},{"key":"3325_CR58","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1124\/mol.111.072801","volume":"80","author":"S Rajagopal","year":"2011","unstructured":"Rajagopal S, Ahn S, Rominger DH, Gowen-MacDonald W, Lam CM, Dewire SM, et al. Quantifying ligand bias at seven-transmembrane receptors. Mol Pharmacol. 2011;80:367\u201377.","journal-title":"Mol Pharmacol"},{"key":"3325_CR59","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00210-008-0260-4","volume":"377","author":"FJ Ehlert","year":"2008","unstructured":"Ehlert FJ. On the analysis of ligand-directed signaling at G protein-coupled receptors. Naunyn Schmiedebergs Arch Pharmacol. 2008;377:549\u201377.","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"3325_CR60","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s10928-013-9306-4","volume":"40","author":"RJ Shannon","year":"2013","unstructured":"Shannon RJ, Carpenter KL, Guilfoyle MR, Helmy A, Hutchinson PJ. Cerebral microdialysis in clinical studies of drugs: pharmacokinetic applications. J Pharmacokinet Pharmacodyn. 2013;40:343\u201358.","journal-title":"J Pharmacokinet Pharmacodyn"},{"key":"3325_CR61","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1124\/dmd.120.000118","volume":"48","author":"WJ Jusko","year":"2020","unstructured":"Jusko WJ, Molins EAG, Ayyar VS. Seeking nonspecific binding: assessing the reliability of tissue dilutions for calculating fraction unbound. Drug Metab Dispos. 2020;48:894\u2013902.","journal-title":"Drug Metab Dispos"},{"key":"3325_CR62","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1208\/s12248-017-0050-3","volume":"19","author":"Y Yamamoto","year":"2017","unstructured":"Yamamoto Y, Danhof M, de Lange ECM. Microdialysis: the key to physiologically based model prediction of human CNS target site concentrations. AAPS J. 2017;19:891\u2013909.","journal-title":"AAPS J"},{"key":"3325_CR63","first-page":"93","volume":"1","author":"AT Shulgin","year":"1975","unstructured":"Shulgin AT, Carter MF. Centrally active phenethylamines. Psychopharmacol Commun. 1975;1:93\u201398.","journal-title":"Psychopharmacol Commun"},{"key":"3325_CR64","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1007\/s00204-020-02836-w","volume":"94","author":"E Pottie","year":"2020","unstructured":"Pottie E, Cannaert A, Stove CP. In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of \u03b2-arrestin 2 recruitment to the serotonin 2A receptor. Arch Toxicol. 2020;94:3449\u201360.","journal-title":"Arch Toxicol"},{"key":"3325_CR65","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/jnc.15570","volume":"162","author":"E Pottie","year":"2022","unstructured":"Pottie E, Stove CP. In vitro assays for the functional characterization of (psychedelic) substances at the serotonin receptor 5-HT2AR. J Neurochem. 2022;162:39\u201359.","journal-title":"J Neurochem"},{"key":"3325_CR66","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.112203","volume":"42","author":"V Lewis","year":"2023","unstructured":"Lewis V, Bonniwell EM, Lanham JK, Ghaffari A, Sheshbaradaran H, Cao AB, et al. A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Cell Rep. 2023;42:112203.","journal-title":"Cell Rep"},{"key":"3325_CR67","doi-asserted-by":"publisher","unstructured":"Gumpper RH, Nichols DE. Chemistry\/structural biology of psychedelic drugs and their receptor(s). Br J Pharmacol. 2024:1\u201315. https:\/\/doi.org\/10.1111\/bph.17361.","DOI":"10.1111\/bph.17361"},{"key":"3325_CR68","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1124\/mol.52.2.259","volume":"52","author":"BL Roth","year":"1997","unstructured":"Roth BL, Shoham M, Choudhary MS, Khan N. Identification of conserved aromatic residues essential for agonist binding and second messenger production at 5-hydroxytryptamine2A receptors. Mol Pharmacol. 1997;52:259\u201366.","journal-title":"Mol Pharmacol"},{"key":"3325_CR69","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1016\/j.cell.2020.08.024","volume":"182","author":"K Kim","year":"2020","unstructured":"Kim K, Che T, Panova O, DiBerto JF, Lyu J, Krumm BE, et al. Structure of a hallucinogen-activated Gq-coupled 5-HT2A serotonin receptor. Cell. 2020;182:1574\u201388.e19.","journal-title":"Cell"},{"key":"3325_CR70","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-025-57956-7","volume":"16","author":"RH Gumpper","year":"2025","unstructured":"Gumpper RH, Jain MK, Kim K, Sun R, Sun N, Xu Z, et al. The structural diversity of psychedelic drug actions revealed. Nat Commun. 2025;16:2734.","journal-title":"Nat Commun"},{"key":"3325_CR71","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1021\/acschemneuro.3c00267","volume":"14","author":"E Pottie","year":"2023","unstructured":"Pottie E, Poulie CBM, Simon IA, Harps\u00f8e K, D\u2019Andrea L, Komarov IV, et al. Structure-activity assessment and in-depth analysis of biased agonism in a set of phenylalkylamine 5-HT2A receptor agonists. ACS Chem Neurosci. 2023;14:2727\u201342.","journal-title":"ACS Chem Neurosci"},{"key":"3325_CR72","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1124\/mol.106.028720","volume":"70","author":"MR Braden","year":"2006","unstructured":"Braden MR, Parrish JC, Naylor JC, Nichols DE. Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists. Mol Pharmacol. 2006;70:1956\u201364.","journal-title":"Mol Pharmacol"},{"key":"3325_CR73","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1124\/mol.107.039255","volume":"72","author":"MR Braden","year":"2007","unstructured":"Braden MR, Nichols DE. Assessment of the roles of serines 5.43(239) and 5.46(242) for binding and potency of agonist ligands at the human serotonin 5-HT2A receptor. Mol Pharmacol. 2007;72:1200\u20139.","journal-title":"Mol Pharmacol"},{"key":"3325_CR74","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.pbb.2007.09.007","volume":"88","author":"WE Fantegrossi","year":"2008","unstructured":"Fantegrossi WE, Reissig CJ, Katz EB, Yarosh HL, Rice KC, Winter JC. Hallucinogen-like effects of N,N-dipropyltryptamine (DPT): possible mediation by serotonin 5-HT1A and 5-HT2A receptors in rodents. Pharmacol Biochem Behav. 2008;88:358\u201365.","journal-title":"Pharmacol Biochem Behav"},{"key":"3325_CR75","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0091-3057(99)00178-1","volume":"65","author":"JC Winter","year":"2000","unstructured":"Winter JC, Filipink RA, Timineri D, Helsley SE, Rabin RA. The paradox of 5-methoxy-N,N-dimethyltryptamine: an indoleamine hallucinogen that induces stimulus control via 5-HT1A receptors. Pharmacol Biochem Behav. 2000;65:75\u201382.","journal-title":"Pharmacol Biochem Behav"},{"key":"3325_CR76","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.pharmthera.2003.11.002","volume":"101","author":"DE Nichols","year":"2004","unstructured":"Nichols DE. Hallucinogens. Pharmacol Ther. 2004;101:131\u201381.","journal-title":"Pharmacol Ther"},{"key":"3325_CR77","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.neuropharm.2011.01.017","volume":"61","author":"AL Halberstadt","year":"2011","unstructured":"Halberstadt AL, Geyer MA. Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology. 2011;61:364\u201381.","journal-title":"Neuropharmacology"},{"key":"3325_CR78","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.euroneuro.2016.05.001","volume":"26","author":"A Rickli","year":"2016","unstructured":"Rickli A, Moning OD, Hoener MC, Liechti ME. Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. Eur Neuropsychopharmacol. 2016;26:1327\u201337.","journal-title":"Eur Neuropsychopharmacol"},{"key":"3325_CR79","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/mp.2012.57","volume":"18","author":"FG Revel","year":"2013","unstructured":"Revel FG, Moreau JL, Pouzet B, Mory R, Bradaia A, Buchy D, et al. A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight. Mol Psychiatry. 2013;18:543\u201356.","journal-title":"Mol Psychiatry"},{"key":"3325_CR80","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.phrs.2016.08.022","volume":"113","author":"D De Gregorio","year":"2016","unstructured":"De Gregorio D, Posa L, Ochoa-Sanchez R, McLaughlin R, Maione S, Comai S, et al. The hallucinogen D-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT1A, D2 and TAAR1 receptors. Pharmacol Res. 2016;113:81\u201391.","journal-title":"Pharmacol Res"},{"key":"3325_CR81","doi-asserted-by":"crossref","first-page":"14148","DOI":"10.3390\/ijms232214148","volume":"23","author":"O Shahar","year":"2022","unstructured":"Shahar O, Botvinnik A, Esh-Zuntz N, Brownstien M, Wolf R, Lotan A, et al. Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 receptors in the head twitch response Induced by 5-hydroxytryptophan and psilocybin: translational implications. Int J Mol Sci. 2022;23:14148.","journal-title":"Int J Mol Sci"},{"key":"3325_CR82","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1038\/s41386-023-01607-2","volume":"48","author":"L Ley","year":"2023","unstructured":"Ley L, Holze F, Arikci D, Becker AM, Straumann I, Klaiber A, et al. Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants. Neuropsychopharmacology. 2023;48:1659\u201367.","journal-title":"Neuropsychopharmacology"},{"key":"3325_CR83","volume":"13","author":"SB Vogt","year":"2023","unstructured":"Vogt SB, Ley L, Erne L, Straumann I, Becker AM, Klaiber A, et al. Acute effects of intravenous DMT in a randomized placebo-controlled study in healthy participants. Transl Psychiatry. 2023;13:172.","journal-title":"Transl Psychiatry"},{"key":"3325_CR84","unstructured":"Hansch CH, Leo A Substituent constants for correlation analysis in chemistry and biology. Wiley: New York (N.Y.), 1979."},{"key":"3325_CR85","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1021\/ci700257y","volume":"47","author":"T Cheng","year":"2007","unstructured":"Cheng T, Zhao Y, Li X, Lin F, Xu Y, Zhang X, et al. Computation of octanol\u2212water partition coefficients by guiding an additive model with knowledge. J Chem Inf Model. 2007;47:2140\u20138.","journal-title":"J Chem Inf Model"},{"key":"3325_CR86","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1602\/neurorx.2.4.541","volume":"2","author":"H Pajouhesh","year":"2005","unstructured":"Pajouhesh H, Lenz GR. Medicinal chemical properties of successful central nervous system drugs. NeuroRx. 2005;2:541\u201353.","journal-title":"NeuroRx"},{"key":"3325_CR87","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","volume":"45","author":"DF Veber","year":"2002","unstructured":"Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002;45:2615\u201323.","journal-title":"J Med Chem"},{"key":"3325_CR88","doi-asserted-by":"crossref","first-page":"6338","DOI":"10.1021\/jm049717d","volume":"47","author":"PD Leeson","year":"2004","unstructured":"Leeson PD, Davis AM. Time-related differences in the physical property profiles of oral drugs. J Med Chem. 2004;47:6338\u201348.","journal-title":"J Med Chem"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41380-025-03325-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-025-03325-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-025-03325-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T10:04:40Z","timestamp":1771409080000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41380-025-03325-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,5]]},"references-count":88,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["3325"],"URL":"https:\/\/doi.org\/10.1038\/s41380-025-03325-1","relation":{},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"value":"1359-4184","type":"print"},{"value":"1476-5578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,5]]},"assertion":[{"value":"3 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 October 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 November 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"MCH is an employee of F. Hoffmann-La Roche; MEL is a consultant for Mind Medicine, Inc. The other authors do not have any conflicts of interest to declare for this study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Animal studies were approved by the NIDA IRP Animal Care and Use Committee (protocol # 23-OSD-37) or the Cantonal Veterinary Office Basel-Stadt (license # 3213_36052).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}