{"entity": "researcher", "timestamp": "2026-08-22T09:17:45.878Z", "family": "Loryan", "given": "Irena", "initials": "I", "orcid": "0000-0002-1557-4416", "affiliations": ["Translational PKPD Group, Department of Pharmaceutical Biosciences, Associate Member of SciLifeLab, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/8373a9e8e10a48b7904075577f7a15e6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/8373a9e8e10a48b7904075577f7a15e6"}}, "publications": [{"entity": "publication", "iuid": "45a835498fbf41c390d679c484b568f2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/45a835498fbf41c390d679c484b568f2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/45a835498fbf41c390d679c484b568f2"}}, "title": "Molecular basis of mood and cognitive adverse events elucidated via a combination of pharmacovigilance data mining and functional enrichment analysis.", "authors": [{"family": "Andronis", "given": "Christos", "initials": "C", "orcid": "0000-0002-6174-579X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d39bce1ca65415e84d55eb343195110.json"}}, {"family": "Silva", "given": "Jo\u00e3o Pedro", "initials": "JP", "orcid": "0000-0002-5656-0897", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cbd2157630cf4708a232260c31918a51.json"}}, {"family": "Lekka", "given": "Eftychia", "initials": "E", "orcid": "0000-0003-4416-0148", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0c3fe371999d4b908c7f1ae1de76c3b9.json"}}, {"family": "Virvilis", "given": "Vassilis", "initials": "V", "orcid": "0000-0003-4573-0501", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9659ff042e9c4c93b72ddea6dbf9d9ec.json"}}, {"family": "Carmo", "given": "Helena", "initials": "H", "orcid": "0000-0002-6650-5285", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/abbb69a5302b45a0824a030ada78c389.json"}}, {"family": "Bampali", "given": "Konstantina", "initials": "K", "orcid": "0000-0001-5063-4675", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5f53bde26287414e871556bce7d6f44f.json"}}, {"family": "Ernst", "given": "Margot", "initials": "M", "orcid": "0000-0002-9809-2649", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d0ef853c1af4955b30e7f2e7ba45745.json"}}, {"family": "Hu", "given": "Yang", "initials": "Y", "orcid": "0000-0002-8702-6654", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bd6b24b1fddd42839186695c2920a747.json"}}, {"family": "Loryan", "given": "Irena", "initials": "I", "orcid": "0000-0002-1557-4416", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8373a9e8e10a48b7904075577f7a15e6.json"}}, {"family": "Richard", "given": "Jacques", "initials": "J", "orcid": "0000-0002-5286-9088", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/08240fcf3bc04e4dbd9326a40448b167.json"}}, {"family": "Carvalho", "given": "F\u00e9lix", "initials": "F", "orcid": "0000-0003-3858-3494", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ba8f1d5c4854156b0270667e8edcdc7.json"}}, {"family": "Savi\u0107", "given": "Miroslav M", "initials": "MM", "orcid": "0000-0002-6934-9193", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f8c93c91a41a460183cc585a1eb63447.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Arch. Toxicol.", "issn": "1432-0738", "volume": "94", "issue": "8", "pages": "2829-2845", "issn-l": "0340-5761"}, "abstract": "Drug-induced Mood- and Cognition-related adverse events (MCAEs) are often only detected during the clinical trial phases of drug development, or even after marketing, thus posing a major safety concern and a challenge for both pharmaceutical companies and clinicians. To fill some gaps in the understanding and elucidate potential biological mechanisms of action frequently associated with MCAEs, we present a unique workflow linking observational population data with the available knowledge at molecular, cellular, and psychopharmacology levels. It is based on statistical analysis of pharmacovigilance reports and subsequent signaling pathway analyses, followed by evidence-based expert manual curation of the outcomes. Our analysis: (a) ranked pharmaceuticals with high occurrence of such adverse events (AEs), based on disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database, and (b) identified 120 associated genes and common pathway nodes possibly underlying MCAEs. Nearly two-thirds of the identified genes were related to immune modulation, which supports the critical involvement of immune cells and their responses in the regulation of the central nervous system function. This finding also means that pharmaceuticals with a negligible central nervous system exposure may induce MCAEs through dysregulation of the peripheral immune system. Knowledge gained through this workflow unravels putative hallmark biological targets and mediators of drug-induced mood and cognitive disorders that need to be further assessed and validated in experimental models. Thereafter, they can be used to substantially improve in silico/in vitro/in vivo tools for predicting these adversities at a preclinical stage.", "doi": "10.1007/s00204-020-02788-1", "pmid": "32504122", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7395038"}, {"db": "pii", "key": "10.1007/s00204-020-02788-1"}], "notes": [], "created": "2026-08-21T11:05:56.904Z", "modified": "2026-08-21T11:05:57.410Z"}, {"entity": "publication", "iuid": "cf3c706e06c742b0b48ded9bd9914f5c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cf3c706e06c742b0b48ded9bd9914f5c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cf3c706e06c742b0b48ded9bd9914f5c"}}, "title": "Rate and extent of mitragynine and 7-hydroxymitragynine blood-brain barrier transport and their intra-brain distribution: the missing link in pharmacodynamic studies.", "authors": [{"family": "Yusof", "given": "Siti R", "initials": "SR", "orcid": "0000-0003-2257-9933", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51e1c006c0464ac49e6d56c716799782.json"}}, {"family": "Mohd Uzid", "given": "Mahathir", "initials": "M"}, {"family": "Teh", "given": "Eng-Huat", "initials": "EH"}, {"family": "Hanapi", "given": "Nur Aziah", "initials": "NA"}, {"family": "Mohideen", "given": "Mazlin", "initials": "M"}, {"family": "Mohamad Arshad", "given": "Ahmad Saifuddin", "initials": "AS"}, {"family": "Mordi", "given": "Mohd Nizam", "initials": "MN"}, {"family": "Loryan", "given": "Irena", "initials": "I", "orcid": "0000-0002-1557-4416", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8373a9e8e10a48b7904075577f7a15e6.json"}}, {"family": "Hammarlund-Udenaes", "given": "Margareta", "initials": "M"}], "type": "journal article", "published": "2019-09-00", "journal": {"title": "Addict Biol", "issn": "1369-1600", "volume": "24", "issue": "5", "pages": "935-945", "issn-l": "1355-6215"}, "abstract": "Mitragyna speciosa is reported to be beneficial for the management of chronic pain and opioid withdrawal in the evolving opioid epidemic. Data on the blood-brain barrier (BBB) transport of mitragynine and 7-hydroxymitragynine, the active compounds of the plant, are still lacking and inconclusive. Here, we present for the first time the rate and the extent of mitragynine and 7-hydroxymitragynine transport across the BBB, with an investigation of their post-BBB intra-brain distribution. We utilized an in vitro BBB model to study the rate of BBB permeation of the compounds and their interaction with efflux transporter P-glycoprotein (P-gp). Mitragynine showed higher apical-to-basolateral (A-B, i.e. blood-to-brain side) permeability than 7-hydroxymitragynine. 7-Hydroxymitragynine showed a tendency to efflux, with efflux ratio (B-A/A-B) of 1.39. Both were found to inhibit the P-gp and are also subject to efflux by the P-gp. Assessment of the extent of BBB transport in vivo in rats from unbound brain to plasma concentration ratios (Kp,uu,brain ) revealed extensive efflux of both compounds, with less than 10 percent of unbound mitragynine and 7-hydroxymitragynine in plasma crossing the BBB. By contrast, the extent of intra-brain distribution was significantly different, with mitragynine having 18-fold higher brain tissue uptake in brain slice assay compared with 7-hydroxymitragynine. Mitragynine showed a moderate capacity to accumulate inside brain parenchymal cells, while 7-hydroxymitragynine showed restricted cellular barrier transport. The presented findings from this systematic investigation of brain pharmacokinetics of mitragynine and 7-hydroxymitragynine are essential for design and interpretation of in vivo experiments aiming to establish exposure-response relationship.", "doi": "10.1111/adb.12661", "pmid": "30088322", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-21T12:16:49.424Z", "modified": "2026-08-21T12:16:49.510Z"}, {"entity": "publication", "iuid": "6c5ffa485ea94474b6166a97a4111ce1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6c5ffa485ea94474b6166a97a4111ce1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6c5ffa485ea94474b6166a97a4111ce1"}}, "title": "Heterogeneous drug tissue binding in brain regions of rats, Alzheimer's patients and controls: impact on translational drug development.", "authors": [{"family": "Gustafsson", "given": "Sofia", "initials": "S"}, {"family": "Sehlin", "given": "Dag", "initials": "D", "orcid": "0000-0002-9430-3859", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/90a93010947247798ba1c003a2892cfa.json"}}, {"family": "Lampa", "given": "Erik", "initials": "E"}, {"family": "Hammarlund-Udenaes", "given": "Margareta", "initials": "M"}, {"family": "Loryan", "given": "Irena", "initials": "I", "orcid": "0000-0002-1557-4416", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8373a9e8e10a48b7904075577f7a15e6.json"}}], "type": "journal article", "published": "2019-03-29", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "9", "issue": "1", "pages": "5308", "issn-l": "2045-2322"}, "abstract": "For preclinical and clinical assessment of therapeutically relevant unbound, free, brain concentrations, the pharmacokinetic parameter fraction of unbound drug in brain (fu,brain) is commonly used to compensate total drug concentrations for nonspecific brain tissue binding (BTB). As, homogenous BTB is assumed between species and in health and disease, rat BTB is routinely used. The impact of Alzheimer's disease (AD) on drug BTB in brain regions of interest (ROI), i.e., fu,brain,ROI, is yet unclear. This study for the first time provides insight into regional drug BTB and the validity of employing rat fu,brain,ROI as a surrogate of human BTB, by investigating five marketed drugs in post-mortem tissue from AD patients (n = 6) and age-matched controls (n = 6). Heterogeneous drug BTB was observed in all within group comparisons independent of disease and species. The findings oppose the assumption of uniform BTB, highlighting the need of case-by-case evaluation of fu,brain,ROI in translational CNS research.", "doi": "10.1038/s41598-019-41828-4", "pmid": "30926941", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6440985"}, {"db": "pii", "key": "10.1038/s41598-019-41828-4"}], "notes": [], "created": "2026-08-21T11:52:42.314Z", "modified": "2026-08-21T11:52:42.382Z"}]}