{"entity": "publication", "iuid": "f21989dcd0a74b20a92ad70a28ded12d", "timestamp": "2026-08-22T06:56:04.156Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f21989dcd0a74b20a92ad70a28ded12d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f21989dcd0a74b20a92ad70a28ded12d"}}, "title": "Funnel metadynamics and behavioral studies reveal complex effect of D2AAK1 ligand on anxiety-like processes.", "authors": [{"family": "Bartuzi", "given": "Damian", "initials": "D"}, {"family": "K\u0119dzierska", "given": "Ewa", "initials": "E"}, {"family": "Targowska-Duda", "given": "Katarzyna M", "initials": "KM"}, {"family": "Kosz\u0142a", "given": "Oliwia", "initials": "O"}, {"family": "Wr\u00f3bel", "given": "Tomasz M", "initials": "TM"}, {"family": "Jademyr", "given": "Simon", "initials": "S"}, {"family": "Karcz", "given": "Tadeusz", "initials": "T"}, {"family": "Szczepa\u0144ska", "given": "Katarzyna", "initials": "K"}, {"family": "St\u0119pnicki", "given": "Piotr", "initials": "P"}, {"family": "Wronikowska-Denysiuk", "given": "Olga", "initials": "O"}, {"family": "Bia\u0142a", "given": "Gra\u017cyna", "initials": "G"}, {"family": "Handzlik", "given": "Jadwiga", "initials": "J"}, {"family": "Kristensen", "given": "Jesper L", "initials": "JL"}, {"family": "Poso", "given": "Antti", "initials": "A"}, {"family": "Kaczor", "given": "Agnieszka A", "initials": "AA"}], "type": "journal article", "published": "2022-12-07", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "12", "issue": "1", "pages": "21192", "issn-l": "2045-2322"}, "abstract": "Anxiety is a troublesome symptom for many patients, especially those suffering from schizophrenia. Its regulation involves serotonin receptors, targeted e.g. by antipsychotics or psychedelics such as LSD. 5-HT2A receptors are known for an extremely long LSD residence time, enabling minute doses to exert a long-lasting effect. In this work, we explore the changes in anxiety-like processes induced by the previously reported antipsychotic, D2AAK1. In vivo studies revealed that the effect of D2AAK1 on the anxiety is mediated through serotonin 5-HT1A and 5-HT2A receptors, and that it is time-dependent (anxiogenic after 30 min, anxiolytic after 60 min) and dose-dependent. The funnel metadynamics simulations suggest complicated ligand-5HT2AR interactions, involving an allosteric site located under the third extracellular loop, which is a possible explanation of the time-dependency. The binding of D2AAK1 at the allosteric site results in a broader opening of the extracellular receptor entry, possibly altering the binding kinetics of orthosteric ligands.", "doi": "10.1038/s41598-022-25478-7", "pmid": "36476619", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9729218"}, {"db": "pii", "key": "10.1038/s41598-022-25478-7"}], "notes": [], "created": "2026-08-21T11:53:50.031Z", "modified": "2026-08-21T11:53:50.044Z"}