Search: id:"swepub:oai:DiVA.org:uu-495620" >
Funnel metadynamics...
Funnel metadynamics and behavioral studies reveal complex effect of D2AAK1 ligand on anxiety-like processes
-
- Bartuzi, Damian (author)
- Uppsala universitet,Beräkningsbiologi och bioinformatik,Science for Life Laboratory, SciLifeLab,Med Univ Lublin, Fac Pharm, Dept Synth, 4A Chodzki St, PL-20093 Lublin, Poland.;Med Univ Lublin, Fac Pharm, Chem Technol Pharmaceut Subst Comp Modeling Lab, 4A Chodzki St, PL-20093 Lublin, Poland.;Uppsala Univ, Dept Cell & Mol Biol, Sci Life Lab, S-75124 Uppsala, Sweden.
-
- Kedzierska, Ewa (author)
- Med Univ Lublin, Fac Pharm, Dept Pharmacol & Pharmacodynam, 4A Chod Ki St, PL-20093 Lublin, Poland.
-
- Targowska-Duda, Katarzyna M. (author)
- Med Univ Lublin, Fac Pharm, Dept Biopharm, 4A Chod Ki St, PL-20093 Lublin, Poland.
-
show more...
-
- Koszla, Oliwia (author)
- Med Univ Lublin, Fac Pharm, Dept Synth, 4A Chodzki St, PL-20093 Lublin, Poland.;Med Univ Lublin, Fac Pharm, Chem Technol Pharmaceut Subst Comp Modeling Lab, 4A Chodzki St, PL-20093 Lublin, Poland.
-
- Wrobel, Tomasz M. (author)
- Med Univ Lublin, Fac Pharm, Dept Synth, 4A Chodzki St, PL-20093 Lublin, Poland.;Med Univ Lublin, Fac Pharm, Chem Technol Pharmaceut Subst Comp Modeling Lab, 4A Chodzki St, PL-20093 Lublin, Poland.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen, Denmark.
-
- Jademyr, Simon (author)
- Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen, Denmark.
-
- Karcz, Tadeusz (author)
- Jagiellonian Univ, Med Coll, Fac Pharm, Dept Technol & Biotechnol Drugs, Medyczna 9, PL-30688 Krakow, Poland.
-
- Szczepanska, Katarzyna (author)
- Jagiellonian Univ, Med Coll, Fac Pharm, Dept Technol & Biotechnol Drugs, Medyczna 9, PL-30688 Krakow, Poland.
-
- Stepnicki, Piotr (author)
- Med Univ Lublin, Fac Pharm, Dept Synth, 4A Chodzki St, PL-20093 Lublin, Poland.;Med Univ Lublin, Fac Pharm, Chem Technol Pharmaceut Subst Comp Modeling Lab, 4A Chodzki St, PL-20093 Lublin, Poland.
-
- Wronikowska-Denysiuk, Olga (author)
- Med Univ Lublin, Fac Biomed, Independent Lab Behav Studies, Chair Biomed Sci, 4A Chod Ki St, PL-20093 Lublin, Poland.
-
- Biala, Grazyna (author)
- Med Univ Lublin, Fac Pharm, Dept Pharmacol & Pharmacodynam, 4A Chod Ki St, PL-20093 Lublin, Poland.
-
- Handzlik, Jadwiga (author)
- Jagiellonian Univ, Med Coll, Fac Pharm, Dept Technol & Biotechnol Drugs, Medyczna 9, PL-30688 Krakow, Poland.
-
- Kristensen, Jesper L. (author)
- Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen, Denmark.
-
- Poso, Antti (author)
- Univ Eastern Finland, Sch Pharm, Yliopistonranta 1,POB 1627, Kuopio 70211, Finland.;Univ Hosp Tubingen, Dept Internal Med 8, Otfried Muller Str 14, D-72076 Tubingen, Germany.;Eberhard Karls Univ Tubingen, Inst Pharmaceut Sci, Dept Pharmaceut & Med Chem, Morgenstelle 8, D-72076 Tubingen, Germany.;Univ Tubingen, Cluster Excellence iFIT EXC 2180 Image Guided & F, D-72076 Tubingen, Germany.;Tubingen Ctr Acad Drug Discovery & Dev TuCAD2, D-72076 Tubingen, Germany.
-
- Kaczor, Agnieszka A. (author)
- Med Univ Lublin, Fac Pharm, Dept Synth, 4A Chodzki St, PL-20093 Lublin, Poland.;Med Univ Lublin, Fac Pharm, Chem Technol Pharmaceut Subst Comp Modeling Lab, 4A Chodzki St, PL-20093 Lublin, Poland.;Univ Eastern Finland, Sch Pharm, Yliopistonranta 1,POB 1627, Kuopio 70211, Finland.
-
show less...
-
(creator_code:org_t)
- 2022-12-07
- 2022
- English.
-
In: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 12:1
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://uu.diva-port... (primary) (Raw object)
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- 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-5HT(2A)R 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Bartuzi, Damian
-
Kedzierska, Ewa
-
Targowska-Duda, ...
-
Koszla, Oliwia
-
Wrobel, Tomasz M ...
-
Jademyr, Simon
-
show more...
-
Karcz, Tadeusz
-
Szczepanska, Kat ...
-
Stepnicki, Piotr
-
Wronikowska-Deny ...
-
Biala, Grazyna
-
Handzlik, Jadwig ...
-
Kristensen, Jesp ...
-
Poso, Antti
-
Kaczor, Agnieszk ...
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Pharmacology and ...
- Articles in the publication
-
Scientific Repor ...
- By the university
-
Uppsala University