A5033794839- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Nitric Oxide and Endothelin Effects
- Pharmacological Receptor Mechanisms and Effects
- Stress Responses and Cortisol
- Neuropeptides and Animal Physiology
- Neuroscience of respiration and sleep
- Neuroinflammation and Neurodegeneration Mechanisms
- Tryptophan and brain disorders
- Ion channel regulation and function
- Neuroendocrine regulation and behavior
- Olfactory and Sensory Function Studies
- Nicotinic Acetylcholine Receptors Study
- Biochemical Analysis and Sensing Techniques
- Treatment of Major Depression
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and Biological Evaluation
- Chemical Reactions and Isotopes
- Photoreceptor and optogenetics research
- Neural dynamics and brain function
- Cancer, Lipids, and Metabolism
- Memory and Neural Mechanisms
- Cholesterol and Lipid Metabolism
- Biochemical effects in animals
Maj Institute of Pharmacology
2016-2024
Polish Academy of Sciences
2016-2024
Institute of Pharmacology
2018
Close structural analogues of 5-carboxamidotryptamine (5-CT) based on the newly discovered indole-imidazole scaffold were synthesized and evaluated to search for a 5-HT<sub>7</sub> receptor agonist higher selectivity.
Cinnabarinic acid (CA) is a kynurenine metabolite that activates mGlu4 metabotropic glutamate receptors. Using highly sensitive ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS-MS) method, we found CA present in trace amounts human brain tissue. levels were largely reduced the prefrontal cortex (PFC) of individuals affected by schizophrenia. This reduction did not correlate with age, sex, duration disease, and type antipsychotic medication might, therefore, represent...
The data concerning antipsychotic-like activity of negative allosteric modulators/antagonists mGlu7 receptors are limited. only available ligands for this receptor MMPIP and ADX71743. In the present studies we used stable cell line expressing it was shown that both compounds dose dependently potentiated forskolin elevated cAMP concentration in T-REx 293 cells, showing their inverse agonist properties. Subsequently, pharmacokinetic were performed. Both given i.p at 10 mg/kg. reached Cmax...
A series of 5-aryl-1-alkylimidazole derivatives was synthesized using the van Leusen multicomponent reaction. The chemotype is first example low-basicity scaffolds exhibiting high affinity for 5-HT7 receptor together with agonist function. chosen lead compounds 3-(1-ethyl-1H-imidazol-5-yl)-5-iodo-1H-indole (AGH-107, 1o, K i = 6 nM, EC50 19 176-fold selectivity over 5-HT1AR) and 1e (5-methoxy analogue, 30 60 nM) exhibited related CNS targets, metabolic stability low toxicity in HEK-293 HepG2...
Metabotropic glutamate receptors and muscarinic M4 have been proposed as novel targets for various brain disorders, including schizophrenia. Both are coupled to Go/i proteins expressed in circuits that important Therefore, their mutual activation may be an effective treatment allow minimizing the doses of ligands required optimal activity.In present studies, subactive mGlu4 activators (LSP4-2022 VU152100, respectively) were administered investigate interaction between animal models...
Following the glutamatergic theory of schizophrenia and based on our previous study regarding antipsychotic-like activity mGlu7 NAMs, we synthesized a new compound library containing 103 members, which were examined for NAM in T-REx 293 cell line expressing recombinant human receptor. Out twenty-two scaffolds examined, active compounds found only within quinazolinone chemotype. 2-(2-Chlorophenyl)-6-(2,3-dimethoxyphenyl)-3-methylquinazolin-4(3H)-one (A9-7, ALX-171, IC50 = 6.14 µM) was...
Learning and memory deficits accompany numerous brain dysfunctions, including schizophrenia Alzheimer's disease (AD), many studies point to the role of nitric oxide (NO) in these processes. The present investigations constitute follow-up our previous research, which we investigated activity NO releasers a selective inhibitor neuronal synthase (nNOS) prevent short-term novel object recognition T-maze. Here, ability compounds induction long-term by MK-801 or scopolamine administration was...
The Morris water maze (MWM) is regarded as one of the most popular tests for detecting spatial memory in rodents. Long-term potentiation and cGMP synthesis seem to be among crucial factors involved this type learning. Muscarinic (M1, M4, M5 receptors) metabotropic glutamate (mGlu) receptors are important targets search antipsychotic drugs with potency treat cognitive disabilities associated disorder. Here, we show that muscarinic receptor activators (VU0357017, VU0152100, VU0238429) an mGlu2...
Negative and cognitive symptoms of schizophrenia contribute to an impaired social professional life for schizophrenic patients, in most cases, these are treatment resistant. Therefore, identification new strategies is sorely needed. Metabotropic glutamate receptors (mGlu) muscarinic (M) acetylcholine have been considered promising targets novel antipsychotics. Among them, mGlu2 M4 subtypes seem be particular importance. In the present study, effect mutual activation was assessed MK-801-based...
MK-801, an NMDA receptor antagonist, and scopolamine, a cholinergic blocker, are widely used as tool compounds to induce learning memory deficits in animal models study schizophrenia or Alzheimer-type dementia (AD), respectively. Memory impairments observed after either acute chronic administration of compound. The present experiments were performed the nitric oxide (NO)-related mechanisms underlying dysfunction induced by (14 days) MK-801 (0.3 mg/kg, i.p.) scopolamine (1 i.p.). levels...
The role of endothelial nitric oxide synthase (eNOS) in the regulation a variety biological processes is well established, and its dysfunction contributes to brain pathologies, including schizophrenia or Alzheimer’s disease (AD). Positive allosteric modulators (PAMs) metabotropic glutamate (mGlu) receptors were shown be effective procognitive compounds, but little known about their impact on eNOS expression stability. Here, we investigated influence acute chronic administration LY487379...
Recent studies revealed that the activation of serotonergic 5-HT1A and muscarinic M1, M4, or M5 receptors prevent MK-801-induced cognitive impairments in animal models. In present study, effectiveness simultaneous at preventing deficits novel object recognition (NOR) Y-maze tests was investigated. Activators (F15599), M1 (VU0357017), M4 (VU0152100), (VU0238429) administered top doses for seven days reversed NOR test, similar to administration subeffective F15599 (0.05 mg/kg) with VU0357017...
Accumulating evidence indicates that early adverse life experiences may be involved in the pathogenesis of Alzheimer's disease (AD). Prenatal stress (PS) can affect brain maturation and neuroimmune metabolic interactions, leading to age-dependent cognitive deficits offspring. However, a multi-faceted cause-and-effect impact PS on development process physiological ageing APPNL-F/NL-F mouse model has not yet been evaluated. We have identified learning memory using male C57BL/6 J (wild type,...
A series of N-skatyltryptamines was synthesized and their affinities for serotonin dopamine receptors were determined. Compounds exhibited activity toward 5-HT1A, 5-HT2A, 5-HT6, D2 receptors. Substitution patterns resulting in affinity/activity switches identified studied using homology modeling. Chosen hits screened to determine metabolism, permeability, hepatotoxicity, CYP inhibition. Several receptor antagonists with additional 5-HT6R antagonist agonist properties identified. The former...