“Targeting Neuroinflammation and Cognitive Decline: First-in-Class Dual Butyrylcholinesterase and p38α Mitogen-Activated Protein Kinase Inhibitors.” J Med Chem. 2025 Aug 28;68(16):17378-17411. doi: 10.1021/acs.jmedchem.5c00933. Epub 2025 Aug 8.PMID: 40779804.
Research
Research topics
Experimental and clinical pharmacokinetics of cardiovascular, antidepressant, anti-inflammatory and antibacterial drugs.
Pharmacokinetics of chiral drugs.
Studies of metabolism and membrane transport mechanisms.
Evaluation of drug pharmacokinetics in inflammatory disease models.
New treatments for sepsis in experimental animal models.
Pharmacokinetic-pharmacodynamic modeling (PK/PD) as a tool in new drug research.
Use of population pharmacokinetics in pharmacotherapy optimization.
Studies of the structure-pharmacokinetic (QSPKR) relationships of new xanthine derivatives.
Biomaterials as potential drug carriers – in vitro and in vivo studies.
Applied methods
High performance liquid chromatography, equilibrium dialysis, ultrafiltration, real-time polymerase chain reaction, ELISA, flow cytometry, isolated perfused organs.
Scientific equipment
HPLC with DAD, electrochemical and spectrofluorimetric detection, LC-MS/MS, real-time DNA detection system (Rotor Gene 3000), capillary electrophoresis apparatus (PACE/MDQ), drug dissolution testing system (flow-through method), perfusion system for isolated organs of small animals (mice, rats), kit for Microdialysis (CMA Microdialysis).
Publications
2025
“Zolpidem suppresses cortical spreading depolarization and protects against ischemia/reperfusion injury and resulting neurological dysfunctions.” Biomed Pharmacother. 2025 Aug;189:118320. doi: 10.1016/j.biopha.2025.118320. Epub 2025 Jul 4.PMID: 40616882.
“Effect of apigenin on seizure susceptibility, parvalbumin immunoreactivity, and GABAA receptor expression in the hippocampal neurons in mice.” Eur J Pharmacol. 2025 Jun 5;996:177548. doi: 10.1016/j.ejphar.2025.177548.
“Sigma-1-targeting multimodal compound HBK-15 reverses memory deficits and restores hippocampal plasticity under NMDA hypofunction.” Neurotherapeutics. 2025 Nov 3:e00774. doi: 10.1016/j.neurot.2025.e00774. Online ahead of print.PMID: 41188153.
“Comprehensive Evaluation of 1H-Isoindole-1,3(2H)-Dione Derivatives: Pharmacokinetic Studies and Analgesic Potential in Various Pain Models.” Int J Mol Sci. 2025 Jun 23;26(13):6026. doi: 10.3390/ijms26136026.PMID: 40649805.
“Effect of SSR504734, a Selective Glycine Transporter Type 1 Inhibitor, on Seizure Thresholds, Neurotransmitter Levels, and Inflammatory Markers in Mice.” ACS Chem Neurosci. 2025 Mar 19;16(6):1210-1226. doi: 10.1021/acschemneuro.5c00039.
“Safirinium Fluorescent “Click” Molecular Probes: Synthesis, CuAAC Reactions, and Microscopic Imaging.” Molecules. 2025 Feb 6;30(3):731. doi: 10.3390/molecules30030731.PMID: 39942837
“Synthesis and Biological Evaluation of Nipecotic Acid Derivatives with Terminally Double-Substituted Allenic Spacers as mGAT4 Inhibitors.” J Med Chem. 2025 Oct 9;68(19):19984-20010. doi: 10.1021
acs.jmedchem.5c00520.
“Advanced pharmacological and pharmacokinetic evaluation of 1,3 dimethylpurine-2,6-dione derivative (GR-14) with prominent mood-modulating activity in rats.” Pharmacol Rep. 2025 Feb;77(1):158-171. doi: 10.1007/s43440-024-00686-2.
“Purine-2,6-dione-based multitarget-directed ligands inhibiting PDE/TRPA1/CHIT1 as a new approach for the treatment of COPD.” Bioorg Chem. 2025 Dec;167:109209. doi: 10.1016/j.bioorg.2025.109209.
“Asiatic acid potentiates the activity of common antidepressant drugs in mice.” Psychopharmacology (Berl). 2025 Dec;242(12):2725-2737. doi: 10.1007/s00213-025-06827-6.
“Discovery of novel hybrid pyrrolidin-2-one derivatives exhibiting potent antiseizure and antinociceptive effects in preclinical models.” Biomed Pharmacother. 2025 Dec;193:118728. doi: 10.1016/j.biopha.2025.118728.
“Influence of dietary supplementation with two distinct probiotic strains, Bifidobacterium longum R0175 and Lacticaseibacillus rhamnosus JB-1, on seizure susceptibility and valproate response: Behavioral and biochemical studies in mice.” Nutrition. 2025 Dec 24;145:113083. doi: 10.1016/j.nut.2025.113083.
“Simultaneous modulation of 5-HT6 and SERT by MM394: a dual-target ligand providing neuroprotection against amyloid-β toxicity, memory preservation, and alleviation of BPSD symptoms.” Pharmacol Biochem Behav. 2026 Jan;258:174128. doi: 10.1016/j.pbb.2025.174128.
2024
“The Role of Pharmacometrics in Advancing the Therapies for Autoimmune Diseases.” Pharmaceutics. 2024 Dec 5;16(12):1559. doi: 10.3390/pharmaceutics16121559.PMID: 39771538 Free article. Review.
“Pharmacokinetics and Quantitative Structure-Pharmacokinetics Relationship Study of Xanthine Derivatives with Antidepressant, Anti-Inflammatory, and Analgesic Activity in Rats.” Świerczek A, Szafarz M, Cios A, Kobierski J, Pociecha K, Attard Saliba D, Chłoń-Rzepa G, Wyska E.Pharmaceutics. 2024 Nov 16;16(11):1463. doi: 10.3390/pharmaceutics16111463.
“Novel Alaninamide Derivatives with Drug-like Potential for Development as Antiseizure and Antinociceptive Therapies─In Vitro and In Vivo Characterization.” Jakubiec M, Abram M, Zagaja M, Andres-Mach M, Szala-Rycaj J, Latacz G, Honkisz-Orzechowska E, Mogilski S, Kubacka M, Szafarz M, Pociecha K, Przejczowska-Pomierny K, Wyska E, Socała K, Nieoczym D, Szulczyk B, Wlaź P, Metcalf CS, Wilcox K, Kamiński RM, Kamiński K.ACS Chem Neurosci. 2024 Jun 5;15(11):2198-2222. doi: 10.1021/acschemneuro.4c00013.
“Discovery and Profiling of New Multimodal Phenylglycinamide Derivatives as Potent Antiseizure and Antinociceptive Drug Candidates.” Jakubiec M, Abram M, Zagaja M, Socała K, Panic V, Latacz G, Mogilski S, Szafarz M, Szala-Rycaj J, Saunders J, West PJ, Nieoczym D, Przejczowska-Pomierny K, Szulczyk B, Krupa A, Wyska E, Wlaź P, Metcalf CS, Wilcox K, Andres-Mach M, Kamiński RM, Kamiński K.ACS Chem Neurosci. 2024 Sep 4;15(17):3228-3256. doi: 10.1021/acschemneuro.4c00438.
“The antidepressant-like and glioprotective effects of the Y2 receptor antagonist SF-11 in the astroglial degeneration model of depression in rats: Involvement of glutamatergic inhibition.” Domin H, Konieczny J, Cieślik P, Pochwat B, Wyska E, Szafarz M, Lenda T, Biała D, Gąsior Ł, Śmiałowska M, Szewczyk B.Behav Brain Res. 2024 Feb 4;457:114729. doi: 10.1016/j.bbr.2023.114729.
“Dual 5-HT6/SERT ligands for mitigating neuropsychiatric symptoms of dementia exerting neuroprotection against amyloid-β toxicity, memory preservation, and antidepressant-like properties.” Siwek A, Marcinkowska M, Głuch-Lutwin M, Mordyl B, Wolak M, Jastrzębska-Więsek M, Wilczyńska-Zawal N, Wyska E, Szafrańska K, Karcz T, Ostrowska O, Bucki A, Kołaczkowski M.Eur J Med Chem. 2024 Sep 5;275:116601. doi: 10.1016/j.ejmech.2024.116601. Epub 2024 Jun 14.PMID: 38901106
“Effect of dietary supplementation with Lactobacillus helveticus R0052 on seizure thresholds and antiseizure potency of sodium valproate in mice.” Wlaź P, Wiater A, Majewska M, Wyska E, Grąz M, Śliwa-Dominiak J, Gapińska N, Socała K.Psychopharmacology (Berl). 2024 Feb;241(2):327-340. doi: 10.1007/s00213-023-06489-2.
2023
“The antidepressant-like and glioprotective effects of the Y2 receptor antagonist SF-11 in the astroglial degeneration model of depression in rats: Involvement of glutamatergic inhibition.” Behav Brain Res. 2023 Oct 21;457:114729. doi: 10.1016/j.bbr.2023.114729.
“Efficacy of the Multi-Target Compound E153 in Relieving Pain and Pruritus of Different Origins.” Pharmaceuticals (Basel). 2023 Oct 17;16(10):1481. doi: 10.3390/ph16101481.
“Anti-inflammatory effects of dexamethasone in COVID-19 patients: Translational population PK/PD modeling and simulation.” Clin Transl Sci. 2023 Sep;16(9):1667-1679. doi: 10.1111/cts.13577.
“Antiplatelet Effects of Selected Xanthine-Based Adenosine A2A and A2B Receptor Antagonists Determined in Rat Blood.” Int J Mol Sci. 2023
“Inhaled pan-phosphodiesterase inhibitors ameliorate ovalbumin-induced airway inflammation and remodeling in murine model of allergic asthma.”Int Immunopharmacol. 2023 Jun;119:110264. doi: 10.1016/j.intimp.2023.110264.
“Anticonvulsant Profile of Selected Medium-Chain Fatty Acids (MCFAs) Co-Administered with Metformin in Mice in Acute and Chronic Treatment.” Molecules. 2023 Apr 29;28(9):3810. doi: 10.3390/molecules28093810.PMID: 37175220
“Pharmacokinetic/Pharmacodynamic Modeling of Dexamethasone Anti-Inflammatory and Immunomodulatory Effects in LPS-Challenged Rats: A Model for Cytokine Release Syndrome.” J Pharmacol Exp Ther. 2023 Mar;384(3):455-472. doi: 10.1124/jpet.122.001477.
“TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice.” Cell Mol Life Sci. 2023 Apr 25;80(5):133. doi: 10.1007/s00018-023-04766-z.PMID: 37185787
“KM-408, a novel phenoxyalkyl derivative as a potential anticonvulsant and analgesic compound for the treatment of neuropathic pain.” Pharmacol Rep. 2023 Feb;75(1):128-165. doi: 10.1007/s43440-022-00431-7.
2022
“Pharmacokinetic/Pharmacodynamic Evaluation of a New Purine-2,6-Dione Derivative in Rodents with Experimental Autoimmune Diseases.” Pharmaceutics. 2022 May 19;14(5):1090. doi: 10.3390/pharmaceutics14051090.
“Pharmacokinetic/Pharmacodynamic Assessment of Selective Phosphodiesterase Inhibitors in a Mouse Model of Autoimmune Hepatitis.” J Pharmacol Exp Ther. 2022 May;381(2):151-163. doi: 10.1124/jpet.121.001004. Epub 2022 Feb 27.
“Pan-Phosphodiesterase Inhibitors Attenuate TGF-β-Induced Pro-Fibrotic Phenotype in Alveolar Epithelial Type II Cells by Downregulating Smad-2 Phosphorylation.” Pharmaceuticals (Basel). 2022 Mar 30;15(4):423. doi: 10.3390/ph15040423.
2021
“Effects of new antiseizure drugs on seizure activity and anxiety-like behavior in adult zebrafish”. Toxicol Appl Pharmacol. 2021 Sep 15;427:115655. doi: 10.1016/j.taap.2021.115655. Epub 2021 Jul 27. PMID: 34329640
“Identification of New Compounds with Anticonvulsant and Antinociceptive Properties in a Group of 3-substituted (2,5-dioxo-pyrrolidin-1-yl)(phenyl)-Acetamides”.
Int J Mol Sci. 2021 Dec 3;22(23):13092. doi: 10.3390/ijms222313092. PMID: 34884898
“Multifunctional Arylsulfone and Arylsulfonamide-Based Ligands with Prominent Mood-Modulating Activity and Benign Safety Profile, Targeting Neuropsychiatric Symptoms of Dementia”. J Med Chem. 2021 Sep 9;64(17):12603-12629. doi: 10.1021/acs.jmedchem.1c00497. Epub 2021 Aug 26. PMID: 34436892
“Synthesis and in vitro evaluation of anti-inflammatory, antioxidant, and anti-fibrotic effects of new 8-aminopurine-2,6-dione-based phosphodiesterase inhibitors as promising anti-asthmatic agents”. Bioorg Chem. 2021 Dec;117:105409. doi: 10.1016/j.bioorg.2021.105409. Epub 2021 Oct 16. PMID: 34749117
“New imidazopyridines with phosphodiesterase 4 and 7 inhibitory activity and their efficacy in animal models of inflammatory and autoimmune diseases”. Eur J Med Chem. 2021 Jan 1;209:112854. doi: 10.1016/j.ejmech.2020.112854. Epub 2020 Sep 19. PMID: 33022582
“A new class of 5-HT1A receptor antagonists with procognitive and antidepressant properties.” Future Med Chem. 2021 Sep;13(18):1497-1514. doi: 10.4155/fmc-2020-0363. Epub 2021 Jul 13. PMID: 34253032
“Anticonvulsant effect of pterostilbene and its influence on the anxiety- and depression-like behavior in the pentetrazol-kindled mice: behavioral, biochemical, and molecular studies.” Psychopharmacology (Berl). 2021 Aug 1. doi: 10.1007/s00213-021-05933-5. Online ahead of print. PMID: 34333674
“PK/PD Modeling of the PDE7 Inhibitor-GRMS-55 in a Mouse Model of Autoimmune Hepatitis.” Pharmaceutics. 2021 Apr 21;13(5):597. doi: 10.3390/pharmaceutics13050597. PMID: 33919375
“Design and Synthesis of Novel Aminoalkanamides Targeting Neurodegeneration and Symptoms of Alzheimer’s Disease.” Curr Med Chem. 2021 Feb 14. doi: 10.2174/0929867328666210215113346. Online ahead of print. PMID: 33588717
“Effects of classic antiseizure drugs on seizure activity and anxiety-like behavior in adult zebrafish.” Toxicol Appl Pharmacol. 2021 Jan 30;415:115429. doi: 10.1016/j.taap.2021.115429. Online ahead of print. PMID: 33524447
“Effect of Ellagic Acid on Seizure Threshold in Two Acute Seizure Tests in Mice.” Molecules. 2021 Aug 10;26(16):4841. doi: 10.3390/molecules26164841. PMID: 34443428
Scientific Collaboration
- Institute of Nuclear Physics, Polish Academy of Sciences
- Department of Animal Physiology, Faculty of Biology and Biotechnology UMCS
- Department of Pharmacokinetic and Therapeutic Therapy, Faculty of Medicine, PUM
Department of Ceramics and Refractory Technology, Faculty of Materials Science and Ceramics,
