A5052115430- Receptor Mechanisms and Signaling
- Mast cells and histamine
- Pharmacological Receptor Mechanisms and Effects
- Neuropeptides and Animal Physiology
- Management and Organizational Practices
- Management Systems and Quality Improvement
- Phenothiazines and Benzothiazines Synthesis and Activities
- Chemical Synthesis and Analysis
- Circadian rhythm and melatonin
- Neuroscience and Neuropharmacology Research
- Consumer Behavior and Market Dynamics
- Nicotinic Acetylcholine Receptors Study
- Asthma and respiratory diseases
- X-ray Diffraction in Crystallography
- Regulation of Appetite and Obesity
- Pain Mechanisms and Treatments
- Computational Drug Discovery Methods
- Neurotransmitter Receptor Influence on Behavior
- Crystallization and Solubility Studies
- Neonatal Health and Biochemistry
- Drug Solubulity and Delivery Systems
- Molecular Sensors and Ion Detection
- Synthesis and Biological Evaluation
- Psychedelics and Drug Studies
- Accounting Theory and Financial Reporting
Maj Institute of Pharmacology
2021-2025
Polish Academy of Sciences
2021-2025
Jagiellonian University
2016-2024
Wojewódzki Szpital Specjalistyczny nr 4 w Bytomiu
2017
Warsaw University of Technology
2015
In an attempt to extend recent studies showing that some clinically evaluated histamine H3 receptor (H3R) antagonists possess nanomolar affinity at sigma-1 receptors (σ1R), we selected 20 representative structures among our previously reported H3R ligands investigate their σRs. Most of the tested compounds interact with both sigma different degrees. However, only six them showed higher toward σ1R than σ2R highest binding preference for 5, 11, and 12. Moreover, all these share a common...
In search of new dual-acting histamine H3/sigma-1 receptor ligands, we designed a series compounds structurally based on highly active in vivo ligands previously studied and described by our team. However, kept mind that within the previous series, pair closely related compounds, KSK67 KSK68, differing only piperazine/piperidine moiety structural core showed significantly different affinity at sigma-1 receptors (σ1Rs). Therefore, first focused an in-depth analysis protonation states...
This study examines the properties of a novel series 4-oxypiperidines designed and synthesized as histamine H3R antagonists/inverse agonists based on structural modification two lead compounds, viz., ADS003 ADS009. The products are intended to maintain high affinity for while simultaneously inhibiting AChE or/and BuChE enzymes. Selected compounds were subjected hH3R radioligand displacement gpH3R functional assays. Some showed nanomolar affinity. most promising compound in naphthalene was...
The pharmacological profile of pitolisant, a histamine H3 receptor antagonist/inverse agonist, indicates that this compound might reduce body weight and metabolic disturbances. Therefore, we studied the influence pitolisant on weight, water sucrose intake as well disturbances in high-fat high-sugar diet-induced obesity model mice. To induce obesity, male CD-1 mice were fed diet consisting 40% fat blend for 14 weeks, 30% solution available ad libitum. Glucose tolerance test was performed at...
Many studies involving compounds that enhance histamine release, such as H3 receptor (H3R) antagonists, have shown efficacy in inhibiting weight gain, but none passed clinical trials. As part of the search for ligands additional properties, aim this study is to evaluate activity reduction gain a rat model excessive eating, well impact on selected metabolic parameters, and number size adipocytes two new H3R KSK-60 KSK-74, which also exert significant affinity at sigma-2 receptor. Compounds...
Background: Numerous studies highlight the critical role that neural histamine plays in feeding behavior, which is controlled by central H3 and H1 receptors. This fundamental motivation for increased interest creating receptor antagonists as anti-obesity medications. On other hand, multiple neurotransmitter systems have been identified pharmacotherapeutic targets obesity, including sigma-2 systems. Interestingly, our previous rat excessive eating model, we demonstrated a significant...
Kainate receptors are a class of ionotropic glutamate that respond to the excitatory neurotransmitter in central nervous system and play an important role development neurodegenerative disorders regulation synaptic function. In current study, we investigated structure- activity relationship series quinoxaline-2,3-diones substituted at N1, 6, 7 positions, as ligands kainate homomeric GluK1-3 GluK5. Pharmacological characterization showed all derivatives obtained exhibited micromolar affinity...
Although the terms "agonist" and "antagonist" have been used to classify sigma-1 receptor (σ1R) ligands, an unambiguous definition of functional activity is often hard. In order determine pharmacological profile σ1R most common method assess their potency alleviate opioid analgesia. It has well established that agonists reduce analgesic activity, while antagonists demonstrated enhance analgesia in different pain models. present study, we evaluated selected ligands using a novel object...
The future of therapy for neurodegenerative diseases (NDs) relies on new strategies targeting multiple pharmacological pathways. Our research led to obtaining the compound AR71 [(E)-3-(3,4,5-trimethoxyphenyl)-1-(4-(3-(piperidin-1-yl)propoxy)phenyl)prop-2-en-1-one], which has high affinity human H
One of the therapeutic approaches in treatment obesity is use histamine H
In an attempt to find new dual acting histamine H3 receptor (H3R) ligands, we designed a series of compounds, structurally based on previously described in our group, highly active and selective human (hH3R) ligand KSK63. As result, 15 obtained compounds show moderate hH3R affinity, the best being compound 17 (hH3R Ki = 518 nM). Docking H3R homology model revealed two possible binding modes, with key interactions retained both cases. selected were tested for antioxidant properties. Compound...
Itch and pain are closely related but distinct sensations that share largely overlapping mediators receptors. We hypothesized the novel, multi-target compound E153 has potential to attenuate pruritus of different origins. After evaluation sigma receptor affinity pharmacokinetic studies, we tested using procedures models pruritus. Additionally, used pharmacological tools, such as PRE-084, RAMH, JNJ 5207852, S1RA, precisely determine role histamine H3 1 receptors in analgesic antipruritic...
Noting the worldwide rapid increase in prevalence of overweight and obesity new effective drugs are now being sought to combat these diseases. Histamine H3 receptor antagonists may represent an therapy as they have been shown modulate histamine synthesis release affect a number other neurotransmitters (norepinephrine, acetylcholine, γ-aminobutyric acid, serotonin, substance P) thus influencing food intake. Based on preliminary studies determining affinity, intrinsic activity, selected...