A5085484473- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Memory and Neural Mechanisms
- Neuroendocrine regulation and behavior
- Synthesis and Biological Evaluation
- Crystallography and molecular interactions
- Stress Responses and Cortisol
- Pharmacogenetics and Drug Metabolism
- Research on Leishmaniasis Studies
- Cyclopropane Reaction Mechanisms
- Photochromic and Fluorescence Chemistry
- Chemical synthesis and pharmacological studies
- Computational Drug Discovery Methods
- Quinazolinone synthesis and applications
- Nicotinic Acetylcholine Receptors Study
- Bioactive Compounds and Antitumor Agents
- Attention Deficit Hyperactivity Disorder
- Cholinesterase and Neurodegenerative Diseases
- Thyroid Disorders and Treatments
- Neuropeptides and Animal Physiology
- Birth, Development, and Health
- Pharmacological Receptor Mechanisms and Effects
University of Vienna
2016-2024
Paracelsus Medical University
2021-2022
University of Belgrade
2013
Animal studies of effort-based choice behavior are being used to model effort-related motivational dysfunctions in humans. With these procedures, animals offered a between high effort instrumental actions leading highly valued reinforcers vs. low effort/low reward options. Several previous have shown that dopamine (DA) uptake inhibitors, including GBR12909, lisdexamfetamine, methylphenidate, and PRX-14040 can reverse the effects vesicular monoamine transport blocker tetrabenazine, which...
Dopamine (DA), the most abundant human brain catecholaminergic neurotransmitter, modulates key behavioral and neurological processes in young senescent brains, including motricity, sleep, attention, emotion, learning memory, social reward-seeking behaviors. The DA transporter (DAT) regulates transsynaptic levels, influencing all these processes. Compounds targeting DAT (e.g., cocaine amphetamines) were historically used to shape mood cognition, but substances typically lead severe negative...
Modafinil is a wake promoting compound with high potential for cognitive enhancement. It targeting the dopamine transporter (DAT) moderate selectivity, thereby leading to reuptake inhibition and increased levels in synaptic cleft. A series of modafinil analogues have been reported so far, but more target-specific remain be discovered. was aim this study synthesize characterize such and, indeed, compounds were showing higher activities on DAT selectivity toward versus serotonin norepinephrine...
Reduced cognitive abilities are often characterized by an impairment of flexibility, i.e. the ability to switch from learned rules or categories that were important in certain contexts different new modalities rule task. Drugs targeting dopamine transporter (DAT) widely used for their potential enhance abilities. However commercially available drugs limited specificity DAT, blocking also noradrenaline and serotonine transporters, can lead unwanted side effects healthy subjects. Therefore, we...
Atypical dopamine reuptake inhibitors, such as modafinil, are used for the treatment of sleeping disorders and investigated potential therapeutics against cocaine addiction cognitive enhancement. Our continuous effort to find modafinil analogues with higher inhibitory activity on selectivity toward transporter (DAT) has previously led promising thiazole-containing derivatives CE-103, CE-111, CE-123, CE-125. Here, we describe synthesis a series compounds based these scaffolds, which resulted...
A design and a convenient approach for the synthesis of novel <i>N</i>-sulfonyl-2-diphenylmethylsulfinylacetamidines have been demonstrated by starting from benzhydrylsulfanylacetic (BSA) acid. This involves sequential amidation with amines, thionation Lawesson's reagent, iminosulfonylation sulfonyl azides, oxidation sulfide fragment hydrogen peroxide. The key step this transformation (reaction thioamides azides) was carried out either in ethanol or absence any solvent. synthesized compounds...
Treatments for cognitive impairments associated with neuropsychiatric disorders, such as attention deficit hyperactivity disorder or narcolepsy, aim at modulating extracellular dopamine levels in the brain. CE-123 (5-((benzhydrylsulfinyl)methyl) thiazole) is a novel modafinil analog improved specificity and efficacy transporter inhibition that improves motivational processes experimental animals. We studied neuropharmacological behavioral effects of S-enantiomer ((S)-CE-123) R-modafinil...
Leishmaniasis is a highly prevalent, yet neglected disease caused by protozoan parasites of the genus Leishmania. In search for newer, safer, and more effective antileishmanial compounds, we herein present study mode action in addition to detailed structural biological characterization LQOF-G6 [N-benzoyl-N'-benzyl-N″-(4-tertbutylphenyl)guanidine]. X-ray crystallography extensive NMR experiments revealed that nearly exclusively adopts Z conformation stabilized an intramolecular hydrogen bond....
The worldwide increase in cognitive decline, both aging and with psychiatric disorders, warrants a search for pharmacological treatment. Although dopaminergic treatment approaches represent major step forward, current dopamine transporter (DAT) inhibitors are not sufficiently specific as they also target other transporters receptors, thus showing unwanted side effects. Herein, we describe an enantiomerically pure, highly DAT inhibitor, S-CE-123, synthetized our laboratory. Following binding...
In the laboratory, long-term social recognition memory in mice is highly susceptible to proactive and retroactive interference. Here we investigate ability of novel designed dopamine re-uptake inhibitors (rac-CE-123 S-CE-123) block interference respectively. Our data shows that administration rac-CE-123 30 min before learning blocks has been experimentally induced at 3 h, but not 6 post learning. contrast S-CE-123 treatment blocked induction Administration failed interfere with both h h....
Previous studies have shown that atypical dopamine-transporter-inhibitors such as modafinil and its analogues modify behavioral cognitive functions in rodents. Here, we tested potential promnestic effects of the novel, more dopamine-transporter selective analogue CE-158 social discrimination memory task male mice. Systemic administration 1 h before learning event prevented impairment social-recognition following retroactive interference 3 after session a juvenile conspecific. This effect was...
Chagas disease (CD) is a neglected tropical parasitic caused by the protozoan Trypanosoma cruzi. Unfortunately, current etiological treatment for CD unsatisfactory, due to high toxicity and low cure efficacy of compounds, mainly during chronic phase this disease. Thus, discovery new drugs urgent. In present study, we report synthesis series guanidines its evaluation in vitro assays determine trypanocidal effects on Tulahuen T. cruzi strain, transfected with β-galactosidase reporter gene,...
Modafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO) not well studied in regard to Hence we its effect spatial memory paradigm possible effects on dentate gyrus long-term potentiation (DG-LTP). Clinically relevant doses of R-MO, vehicle dimethyl sulfoxide (DMSO) or saline were administered three days during the hole-board test vivo DG-LTP. Synaptic levels dopamine receptors D1R, D2R, transporter (DAT),...
Oxytocin (OT) and vasopressin (VP) are related neuropeptides that regulate many biological processes. In humans, OT VP act via four G protein-coupled receptors, OTR, V1aR, V1bR, V2R (VPRs), which associated with several disorders. To investigate the therapeutic potential of these particularly in receptor-dense areas brain, molecular probes a high temporal spatial resolution required. Such spatiotemporal can be achieved by incorporating photochromic moieties into VP. Here, we report design,...
Maternal separation (MS) is a key contributor to neurodevelopmental disorders, including learning disabilities. To test the hypothesis that dopamine signaling major factor in this, an atypical new transporter (DAT) inhibitor, CE-123, was assessed for its potential counteract MS-induced spatial and memory deficit male female rats. Hence, neonatal rats (postnatal day (PND)1 21) were exposed MS (180 min/day). Next, acquisition of (Barnes maze task) expression D1 receptor, (DAT), neuronal...