Magdalena Bujalska-Zadrozny

Medical University of Warsaw · Department of Pharmacodynamics

In recent years, a series of articles has been published concerning magnetic resonance imaging (MRI) studies in a group of patients exposed to manganism, specifically factory workers, welders, and individuals with liver diseases, as well as those abusing home-produced ephedrone. Some potential symptoms of manganese toxicity include motor disturbanc...

Two polyphenols–hyperoside (HYP) and protocatechuic acid (PCA) were reported to exert antidepressant activity in rodents after acute treatment. Our previous study also showed that this activity might have been influenced by the monoaminergic system and the upregulation of the brain-derived neurotropic factor (BDNF) level. A very long-term pharmacol...

Arylpiperazines represent one of the most important classes of 5-HT1AR ligands and have attracted considerable interests for their versatile properties in chemistry and pharmacology, leading to the research of new derivatives that has been focused on the modification of one or more portions of such pharmacophore. An efficient protocol for the synth...

One of the factors that increase the effectiveness of the pharmacotherapy used in patients abusing various types of new psychoactive substances (NPSs) is the proper functioning of the liver. However, the articles published to date on NPS hepatotoxicity only address non-specific hepatic parameters. The aim of this manuscript was to review three adva...

In recent months, there has been a new trend involving the consumption of Amanita muscaria. The aim of this article was to investigate the reasons for consumption, the form taken and the adverse symptoms that were indicated by those consuming Amanita muscaria. After analysing 5600 comments, 684 people were included in the study, who, in social medi...

A series of 15 new derivatives of 6-acetyl-7-hydroxy-4-methylcoumarin containing a piperazine group were designed with the help of computational methods and were synthesized to study their affinity for the serotonin 5-HT1A and 5-HT2A receptors. Among them, 6-acetyl-7-{4-[4-(3-bromophenyl)piperazin-1-yl]butoxy}-4-methylchromen-2-one (4) and 6-acetyl...

Cannabinoid receptor type 2 (CB2) is a very promising therapeutic target for a variety of potential indications. However, despite the existence of multiple high affinity CB2 ligands, none have yet been approved as a drug. Therefore, it would be beneficial to explore new chemotypes of CB2 ligands. The recent elucidation of CB2 tertiary structure all...

Cannabinoid receptor type 1 (CB1) is an important modulator of many key physiological functions and thus a compelling molecular target. However, safe CB1 targeting is a non-trivial task. In recent years, there has been a surge of data indicating that drugs successfully used in the clinic for years (e.g. paracetamol) show CB1 activity. Moreover, the...

In this work we strived to determine whether endocannabinoid system activity could account for the differences in acute inflammatory pain sensitivity in mouse lines selected for high (HA) and low (LA) swim-stress-induced analgesia (SSIA). Mice received intraplantar injections of 5% formalin and the intensity of nocifensive behaviours was scored. To...

A new series of 5-norbornene-2-carboxamide derivatives was prepared and their affinities to the 5-HT1A, 5-HT2A, and 5-HT2C receptors were evaluated and compared to a previously synthesized series of derivatives characterized by exo-N-hydroxy-5-norbornene-2,3-dicarboximidenu-cleus, in order to identify selective ligands for the above-mentioned subty...

In recent years, an increase in the problem of polypharmacotherapy in psychiatric patients has been observed, including the widespread problem of groups of people taking new psychoactive substances. One reason for this problem may be the poor knowledge of pharmacological interactions in psychiatry. The aim of this study was to explore the opinions...

Objectives: It has been reported that matrix metalloproteinase, MMP-3 may play a significant role in the pathophysiology of mental disorders. However, there are no data on the level of MMP-3 in people suffering from schizophrenia, or its influence on the mental state of these people. The aim of this study was to investigate the effect of an antips...

Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side...

The effectiveness of opioids in the treatment of neuropathic pain is limited. It was demonstrated that magnesium ions (Mg2+), physiological antagonists of N-methyl-D-aspartate receptor (NMDAR), increase opioid analgesia in chronic pain. Our study aimed to determine the molecular mechanism of this action. Early data indicate the cross-regulation of...

Background Numerous case reports describe manganese encephalopathy in patients using ephedrone (methcathinone). The aim of this narrative review of case reports was to relate manganese ion concentrations in peripheral blood to the reported neurological deficits. Methods International databases, including Thomson (Web of Knowledge), PubMed/Medline,...

Background: In recent years, the observed frequency of hospitalization of patients taking mephedrone with other psychoactive substances has increased. There are no data in the literature on the effect of mephedrone use on liver function in patients, including the frequency of HCV infection. We have analysed the impact of taking mephedrone together...

Tapentadol, an analgesic with a dual mechanism of action, involving both μ-opioid receptor agonism and noradrenaline reuptake inhibition (MOP-NRI), was designed for the treatment of moderate to severe pain. However, the widely acknowledged risk of analgesic tolerance and development of physical dependence following sustained opioid use may hinder t...

Recent studies have shown that the knowledge of pharmacological interaction databases in global psychiatry is negligible. The frequency of hospitalizations in the case of patients taking new psychoactive substances along with other drugs continues to increase, very often resulting in the need for polypharmacotherapy. The aim of our research was to...

The development of alcohol dependence and depression is determined by various genetic and environmental factors. In the presented study, we used high analgesia (HA) and low analgesia (LA) mouse lines, characterized by different endogenous opioid system activity and divergent blood–brain barrier permeability, to determine the influence of cross-fost...

One of the key strategies for effective pain management involves delaying analgesic tolerance. Early clinical reports indicate an extraordinary effectiveness of off-label disulfiram—an agent designed for alcohol use disorder—in potentiating opioid analgesia and abrogation of tolerance. Our study aimed to determine whether sustained µ-opioid signali...

Purpose Optimal glycemic control is crucial for proper wound healing in patients with diabetes. However, it is not clear whether other antidiabetic drugs support wound healing in mechanisms different from the normalization of blood glucose control. We assessed the effect of insulin and metformin administration on the wound healing process in rats w...

Background: In recent years, an increase in the frequency of hospitalizations of patients taking newer and newer psychoactive substances has been observed around the world. Each year, authors publish case reports of patients who consumed previously unknown NPS. Most publications of this type concern the period between 2014 and 2016. However, no pub...

Background Magnesium ions (Mg ²⁺ ) increase and prolong opioid analgesia in chronic and acute pain. The nature of this synergistic analgesic interaction has not yet been explained. Our aim was to investigate whether Mg ²⁺ alter tramadol pharmacokinetics. Our secondary goal was to assess the safety of the combination. Methods Tramadol was administe...

Sample preparation procedure Chromatographic conditions Instruments and chemicals TABLE S1 - Method validation summary TABLE S2 - The accuracy and precision of the tramadol determination in plasma samples TABLE S3 - The accuracy and precision of the O-desmethyltramadol determination in plasma samples TABLE S4 - Stability of analytes in plasma e...

We have designed and synthesized a series of 60 new 5- and 7-hydroxycoumarin derivatives bearing the piperazine moiety with the expected binding to 5-HT1A and 5-HT2A receptors. Molecular docking of all investigated compounds revealed subnanomolar estimates of 5-HT1AR Ki for three ligands and 5-HT2AR Ki for one ligand as well as numerous low nanomol...

A new series of norbornene and exo-N-hydroxy-7-oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboximide derivatives was prepared, and their affinities to the 5-HT1A , 5-HT2A , and 5-HT2C receptors were evaluated and compared with a previously synthesized series of derivatives characterized by the same nuclei, to identify selective ligands for the subtype rece...

Brain-derived neurotrophic factor (BDNF) plays an important role in processes associated with neuroplasticity and neuroprotection. Evidence suggests that decreased BDNF levels in the central nervous system (CNS) represent a mechanism underlying the development of mood disorders. We hypothesize that both congenital and traumatic brain injury (mTBI)-...

Struggle with addiction to at least two substances, particularly alcohol and opioids, is a common phenomenon these days. Indeed, narcotic drug abuse people also suffer from extensive alcohol consumption, as this depressant strongly augments opioids intake. As it is thought that to stop drinking is easier than to stop taking drugs, the first step to...

Opioids are the gold standard drugs for the treatment of acute and chronic severe pain, although their serious side effects constitute a big limitation. In the search for new and safer drugs, 5-HT1AR agonists are emerging as potential candidates in pain relief therapy. In this work, we evaluated the affinity and activity of enantiomers of the two n...

Affecting over 320 million people around the world, depression has become a formidable challenge for modern medicine. In addition, an increasing number of studies cast doubt on the monoamine theory of depressive disorder and, worryingly, antidepressant medications only significantly benefit patients with severe depression. Thus, it is not surprisin...

Objectives: The purpose of this research was to investigate the effectiveness of the methadone programme in a group of patients taking mephedrone with heroin. Methods: The research involved 230 people who took part in the methadone programme between 2010 and 2019: 101 people on a mephedrone binge and taking heroin and 129 people addicted to heroin....

The behavioral responses exerted by spinal administration of the opioid-neurotensin hybrid peptide, PK23, were studied in adult male rats. The antinociceptive effect upon exposure to a thermal stimulus, as well as tolerance development, was assessed in an acute pain model. The PK23 chimera at a dose of 10 nmol/rat produced a potent pain-relieving e...

Molecular docking studies using appropriate 5-HT1A, 5-HT2A and D2 receptors models were used to design sixteen new 5-hydroxycoumarin derivatives with piperazine moiety (3-18). The microwave radiation have been used to synthesize them and their structures have been confirmed using mass spectrometry, ¹H and ¹³C NMR. All newly prepared derivatives wer...

Background: Despite solutions presented by the European Union and national regulations introduced by many countries, the problem of mephedrone (4-MMC) is growing. Objectives: The aim of this study was to investigate the effect of regular mephedrone intake with other psychoactive substances on the clinical picture of patients, including self-harms a...

Four 2‐(1H‐indol‐3‐yl)ethylthiourea derivatives were prepared by condensation of 2‐(1H‐indol‐3‐yl)ethanamine with the corresponding aryl/alkylisothiocyanates in a medium‐polarity solvent. Their structures were confirmed by spectral techniques, and the molecular structure of 3 was determined by X‐ray crystal analysis. For all derivatives, the bindin...

Objectives: In recent years, an increase in the frequency of hospitalisations of patients on a mephedrone binge has been observed. The literature lacks data on the optimisation of methadone treatment in this group of people. Methods: The study included 601 patients who took mephedrone on a regular basis between 2010 and 2018. Based on the pharmacol...

Bidirectional selection of mice for high (HA) and low (LA) swim stress-induced analgesia (SSIA) is associated with a divergent response to opioids. In the current study, we investigated whether the genetic divergence in opioid system activity between HA and LA mice also affects cannabinoid sensitivity. Additionally, we also investigated whether the...

Hybrid compounds (also known as chimeras, designed multiple ligands, bivalent compounds) are chemical units where two active components, usually possessing affinity and selectivity for distinct molecular targets, are combined as a single chemical entity. The rationale for using a chimeric approach is well documented as such novel drugs are characte...

Mice selected for high (HA) and low (LA) swim stress-induced analgesia (SSIA) are a unique model for studying the genetic background of this phenomenon. HA and LA mice show substantial differences in the magnitude of the antinociceptive response to stress and when treated with exogenous opioids. However, the direct cause underplaying this distincti...

Background: Chronic hyperalgesia and allodynia associated with progressive damage of peripheral neurons are the most prevalent complications of diabetes mellitus. Plants belonging to the family of Oleaceae were traditionally used in folk medicine for the management of diabetes. Hypothesis/purpose: The aim of this study was to investigate whether...

The concentrations of copper and zinc in the tissues of alcohol-addicted people can significantly correlate with the variables describing their mental state. Studies on the homeostasis of zinc in alcohol-dependent patients have often been characterized by low hypozincemia detection. This may be caused by a low content of zinc in blood serum (1%) co...

Good glycemic control is crucial for the proper wound healing in diabetes. It is not clear whether there is any additional effect on wound healing of any antidiabetic drugs beyond improvement in glucose control. We conducted an experimental study aiming at assessing the effect of insulin and metformin on the wound healing. The study was performed i...

Background: Participation in a clinical trial significantly shortens waiting time associated with receiving specialist care. Furthermore, it may be the case that, through clinical trials, subjects can access medicines that are not typically available in Poland. Objectives: The aim of this study was to determine the opinions of oncological patien...

In this study, we determined the antihyperalgesic and anti-inflammatory activity of AA3052, a novel opioid-substance P hybrid peptide in a rat Complete Freund’s adjuvant (CFA) inflammatory pain model. Central antinociceptive activity of AA3052 was assessed after intracerebroventricular injection using plantar and Randall-Selitto assays. The antinoc...

Taking opioids is often accompanied by the development of dependence. Unfortunately, treatment of opioid dependence is difficult, particularly because of codependence - for example, on alcohol or other drugs of abuse. In the presented study, we analyzed the potential influence of disulfiram, a drug used to aid the management of alcoholism, on opioi...

Background: Studies on the homeostasis of magnesium in alcohol-dependent patients have often been characterized by low hypomagnesemia detection rates. This may be due to the fact that the content of magnesium in blood serum constitutes only 1% of the average magnesium level within the human body. However, the concentration of ionized magnesium is...

The opioid system modulates the central reinforcing effects of ethanol and participates in the etiology of addiction. However, the pharmacotherapy of ethanol dependence targeted on the opioid system is little effective and varies due to individual patients' sensitivity. In the present study, we used two mouse lines with high (HA) and low (LA) activ...

Many psychopathological symptoms, including schizophrenia, can be associated with magnesium metabolism disturbances. In the literature, contradictory data exist regarding magnesium levels in patients with this disorder. However, this situation might be caused by determination of extracellular concentration of magnesium; although, this is mainly an...

The neuroprotective role of the endogenous opioid system in the pathophysiological sequelae of brain injury remains largely ambiguous. Noteworthy, almost no data is available on how its genetically determined activity influences the outcome of mild traumatic brain injury. Thus, the aim of our study was to examine the effect of opioid receptor block...

A search of new analgesic and anti-inflammatory agents is still ongoing. It is well known that an activation of the leukotriene (LT) synthesis is involved in pain signaling. LTs belong to a class of potent proinflammatory mediators that are biosynthesized from arachidonic acid (AA) inter alia by 5-lipoxygenase (5-LOX) enzyme in association with 5-L...

Tuberculosis remains a growing threat of infectious diseases of twenty-first century. An attempt to find new antituberculosis agents was made especially to treat multidrug-resistant and extensively drug-resistant tuberculosis. One of the most promising drugs is bedaquiline - a new drug approved by Food and Drug Administration (FDA) and by the Europ...

Aim The aim of the study was to assess patient knowledge on reporting of adverse drug reactions. Materials and methods A prospective study was conducted among 200 patients. The study was based on an original survey composed of 15 single- and multiple-choice questions. The study involved individuals who have experienced adverse reactions as well as...

Vancomycin has been a predominant treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections for decades. However, growing reservations about its efficacy led to an urgent need for new antibiotics effective against MRSA and other drug-resistant Staphylococcus aureus strains. This review covers three new anti-MRSA antibiotics that h...

Cannabinoids are still classified as illegal psychoactive drugs despite their broad and increasingly acknowledged therapeutic potential. These substances are most famous for their wide recreational use, particularly among young adults to either alter the state of consciousness, intensify pleasure induced by other psychoactive substances or as an al...

Opioids are increasingly used in alleviating pain, including cancer-related pain and postoperative pain. Unfortunately, the development of tolerance, the resistance of neuropathic pain on opioid analgesia or other undesirable effects may limit their utility. In order to reduce opioid doses, and thereby to avoid the risk of side effects and sudden d...

Purpose As previously reported, magnesium sulphate administered parenterally significantly increased an opioid antinociception in different kinds of pain. Since the typical form of magnesium salts are poorly and slowly absorbed from the gastrointestinal tract we examined whether their micronized form could increase opioids induced antinociception....

Supporting data for the manuscript. This file contains Tables: A, B, C, D, E, F. (DOCX)

Suicides constitute a serious public health issue worldwide. The number of suicide victims has been increasing over the years. Susceptibility to suicidal behaviour depends on the interaction of a number of factors. The reasons for taking a decision on committing suicide may objectively seem prosaic, and yet, according to the victim, cannot be resol...

The aim of this study was designed to examine the rate of occurrence of antiepileptic drug overdose in 2002 and 2012 in Cracow, Poland, and analyze the demographics and clinical features of the patients Antiepileptic drugs (AEDs) intoxication. A retrospective study included all the patients admitted in to the Toxicology Units in Cracow for AED into...

We investigated the association between serum valproic acid (VPA) levels and clinical conditions in patients after acute intoxication with this drug. We performed a retrospective study of cases of VPA intoxications hospitalized in Toxicology Unit in Cracow in 2 years of observation. The study included 26 patients (age: 35.69 ± 12.93 years). In all...

Hyponatremia, i.e. reduction of sodium level in the blood plasma below 135 mmol/L, is one of the most common electrolyte disorders occurring in people addicted to alcohol. Since sodium is one of the main bioelements, which is responsible for proper neuromuscular excitability maintenance and contributes in nerve impulses conduction, sodium balance d...

Objectives Esculetin (6,7-dihydroxycoumarin) is a natural coumarin with anti-oxidant, anti-inflammatory and anti-nociceptive activity. It acts as a potent inhibitor of lipoxygenases (5-LOX and 12-LOX) and decreases the production of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9). Because both inhibition of lipoxygenases and inhibition of matrix...

Background: The histamine H4 receptor (H4R) has attracted a lot of attention in terms of its role in antinociception. The N-Methyl-d-aspartic acid (NMDA) receptor is a well-characterized participant in pain pathways. However, it's influence on H4R signaling is poorly understood. Thus, in the present study we investigated the effect of a selective...

The search for a miracle drug that would help to alleviate multiple ailments, dates back many thousands of years before our era and continues until today. Various techniques have been used to obtain a formulation, that would give the desired therapeutic effect. The most popular approach includes drug coctails and multicomponent drugs. Polytherapy i...

The design of novel drugs for pain relief with improved analgesic properties and diminished side effect induction profile still remains a challenging pursuit. Tolerance is one of the most burdensome phenomena that may hamper ongoing opioid therapy, especially in chronic pain patients. Therefore, a promising strategy of hybridizing two pharmacophore...

Hybrid compounds are suggested to be a more effective remedy for treatment of various diseases than combination therapy, since the attenuation or total disappearance of side effects, typically induced by a single moiety, can be observed. This is of great importance, especially when we consider problems resulting from the use of opioid analgesics. H...

Leukotrienes (LTs) belong to pro-inflammatory mediators that are biosynthesized from arachidonic acid (AA), inter alia, by 5-lipoxygenase (5-LOX) enzyme in association with 5-LOX-activating protein (FLAP). An activation of LTs synthesis pathway occurs during the development and maintenance of numerous diseases such as asthma, anaphylactic shock, al...

The search for new drugs for cancer pain management has been a long-standing goal in basic and clinical research. Classical opioid drugs exert their primary antinociceptive effect upon activating opioid receptors located in the central nervous system. A substantial body of evidence points to the relevance of peripheral opioid receptors as potential...

Background: Neuropathic pain is still one of the most difficult pain states to be treated due to the lack of effective drugs. Although the mechanism of action of antiepileptic drugs in alleviating neuropathic pain is not fully understood, it is believed that the bases for both diseases are similar pathophysiologic disturbances. Therefore, in this...

Chronic kidney disease (CKD) is often observed among patients with type 2 diabetes mellitus (T2DM) and diabetic foot (DF) leading to end stage renal disease. The aim of this pilot study was to determine genetic and environmental factors involved in the etiology of CKD among patients with DF. The following polymorphisms were studied: rs1800469, rs75...

Background: The opioid system in the gastrointestinal (GI) tract plays an important physiological role, but is also responsible for the side effect of opioid drugs, including troublesome constipation in chronic pain treatment. The aim of this study was to characterize and validate a new mouse model to study the effects of opioid agonists and antag...

The objective of this paper is to review and summarize the antimicrobial efficacy of the acyldepsipeptides and to indicate the prospects of the therapeutic values of these compounds. This work is enriched by the description of the mutations within the clpP1clpP2 and clpP3clpP4 operons of Streptomyces lividans, which are considered to be the potenti...

The vast therapeutic potential of cannabinoids of both synthetic and plant-derived origins currently makes these compounds the focus of a growing interest. Although cannabinoids are still illicit drugs, their possible clinical usefulness, including treatment of acute or neuropathic pain, have been suggested by several studies. In addition, some obs...

Several neurotransmitter and neuromodulatory systems can control physiological glutamatergic activity. For example, opioid receptor ligands were shown to partially inhibit N-methyl-D-aspartic acid (NMDA) receptor-dependent glutamatergic excitotoxicity. Also, the endogenous tridecapeptide neurotensin (NT) was found to modulate excessive glutamate re...

Staniszewska Anna, Korczak Anna, Juszczyk Grzegorz, Duda-Zalewska Aneta, Olejniczak Dominik, Dąbrowska-Bender Marta, Bujalska-Zadrożny Magdalena. Wiedza kursantów ośrodków szkolenia kierowców odnośnie użycia automatycznego defibrylatora zewnętrznego (AED) w trakcie akcji ratunkowej = Students knowledge of driver training center on the use an Automa...

Some studies suggest that 5-lipoxygenase (5-LOX) inhibition or leukotriene receptor antagonism might effectively attenuate different kinds of pain. In the present study, we decided to investigate whether esculetin, which - among other properties - is a potent inhibitor of 5-LOX, possess analgesic activity in acute non-inflammatory pain and acute in...

As previously reported, magnesium ions (Mg(2+)) administered in relatively low doses markedly potentiated opioid analgesia in neuropathic pain, in which the effectiveness of opioids is limited. Considering that Mg(2+) behaves like an N-methyl-D-aspartate receptor antagonist, the effect of this ion on the analgesic action of morphine was compared wi...