Andrzej Pilc
Jagiellonian University, Drug Management, Faculty Member
- Polish Academy of Sciences, Institute of Pharmacology, Faculty Memberadd
- Main research interest lies in the studies of the mechanism of action of antidepressant/anxiolytic/antipsychotic dru... moreMain research interest lies in the studies of the mechanism of action of antidepressant/anxiolytic/antipsychotic drugs, including the involvement of mGlu or GABA B receptor ligands as well as in the development of new psychotropic substancesedit
This article presents a review of the interactions between zinc and glutamate system in the pathophysiology and treatment of depression.
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The aim of the present study was to determine whether S-4-carboxy-3-hydroxyphenylglycine (S)-4C3HPG, a mixed group I glutamate metabotropic receptor antagonist and a group II agonist, attenuated parkinsonian-like muscle rigidity in rats.... more
The aim of the present study was to determine whether S-4-carboxy-3-hydroxyphenylglycine (S)-4C3HPG, a mixed group I glutamate metabotropic receptor antagonist and a group II agonist, attenuated parkinsonian-like muscle rigidity in rats. Muscle tone was examined using a combined mechano and electromyographic method, which measured simultaneously the muscle resistance (MMG) of the rat's hind foot to passive extension and flexion in the ankle joint and the electromyographic activity (EMG) of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was induced by pretreatment with haloperidol (1 mg/kg i.p.). (S)-4C3HPG injected in doses of 5 and 15 microg/0.5 microl bilaterally, into the rostral region of the striatum, decreased both the haloperidol-induced muscle rigidity (MMG) and the enhanced electromyographic activity (EMG). The present results suggest that blockade of mGluR1 receptors and/or activation of mGluR2 ones, localized in the rostral part of the striatum, may be responsible for the anti-parkinsonian effect of (S)-4C3HPG.
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Broad evidence indicates that modulation of the glutamatergic system could be an efficient way to achieve antidepressant activity. Metabotropic glutamate receptor (mGlu receptor) ligands seem to be promising agents to treat several... more
Broad evidence indicates that modulation of the glutamatergic system could be an efficient way to achieve antidepressant activity. Metabotropic glutamate receptor (mGlu receptor) ligands seem to be promising agents to treat several central nervous system disorders, including psychiatric ones. The aim of our study was to investigate potential antidepressant-like activity of the first, selective, and bio-available mGlu7 receptor agonist, AMN082 (N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride), in wild-type (WT) and mGlu7 receptor knock-out (KO) mice. The forced swim test (FST) and the tail suspension test (TST) in mice were used to assess antidepressant-like activity of AMN082. We found that AMN082, administered IP, induced a dose-dependent decrease in the immobility time of WT animals in the FST and TST, suggesting antidepressant-like potency of an mGlu7 receptor agonist. Moreover, AMN082 did not change the behaviour of mGlu7 receptor KO mice compared to WT littermates in the TST, while imipramine, used as a reference control, significantly reduced their immobility, indicating an mGlu7 receptor-dependent mechanism of the antidepressant-like activity of AMN082. However, at high doses, AMN082 significantly decreased spontaneous locomotor activity of both mGlu7 receptor KO mice and WT control animals, suggesting off-target activity of AMN082 resulting in hypo-locomotion. These results strongly suggest that activation of the mGlu7 receptor elicits antidepressant-like effects.
Research Interests: Pharmacology, Psychopharmacology, Animal Behavior, Depression, Biology, and 15 moreMedicine, Mice, Animals, Male, Central Nervous System, Genotype, Analysis of Variance, Forced Swim Test, Locomotor Activity, Knock out, Imipramine, Agonist, Motor activity, Psychology and Cognitive Sciences, and Medical and Health Sciences
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Hetzenauer A, Corti C, Herdy S, Corsi M, Ferraguti F, Singewald N (2008) Individual contribution of metabotropic glutamate receptor (mGlu) 2 and 3 to c-Fos expression pattern evoked by mGlu2/3 antagonism. Psychopharmacology (Berl) 201: 1–13. Hughes JR (2009) Alcohol withdrawal seizures. Epilepsy ...more
Publisher Summary This chapter discusses a study to investigate changes in alpha2-adrenoreceptor density after chronic treatment with imipramine. Adult Wistar rats were injected with imipramine 10 mg/kg i.p. for 21 days. Twenty four hours... more
Publisher Summary This chapter discusses a study to investigate changes in alpha2-adrenoreceptor density after chronic treatment with imipramine. Adult Wistar rats were injected with imipramine 10 mg/kg i.p. for 21 days. Twenty four hours after the last injection, rats were killed and 3-H-clonidine binding to crude synaptosomal fraction from cortex and mesencephalon was investigated. The specific binding of 3-H-clonidine was significantly depressed in the cerebral cortex (by 25%). The decrease of 3-H-clonidine binding was because of depression of Bmax, from 0.21 pmola/mg prot to 0.12 pmola/mg prot, without significant changes in the dissociation constant. In the mesencephalon, however, an increase of 3-H-clonidine binding (by 30%) was observed. In this case, the Bmax value was increased from 0.078 pmola/mg prot to 0.094 pmola/mg prot. The dissociation constant was decreased from 6.02 to 3.77 nM. The results show that after prolonged treatment with an antidepressant drug, in some brain regions, an increase and decrease in alpha2-adrenoreceptor density occurs, which may lead to hyper and hyposensitivity.
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The role of group II metabotropic glutamate receptors (mGlu receptors) in mechanisms of long-term potentiation was investigated by analysis of excitatory postsynaptic field potentials of the CA1 region in rat hippocampal slices. The... more
The role of group II metabotropic glutamate receptors (mGlu receptors) in mechanisms of long-term potentiation was investigated by analysis of excitatory postsynaptic field potentials of the CA1 region in rat hippocampal slices. The application of the group II agonists (2S,1′S,2′S)-2-(carboxycyclopropyl) glycine (L-CCG-I) and (2S,1′R,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl) glycine (DCG IV) resulted in a dose-dependent reduction of long term potentiation in the concentration range
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... mGluR (2S,1'R, 2'R,3'R)-2-(2,3-dikarboksycyklopropylo)glicyna (DCG-IV), jak również 4C3HPG, oraz (2S,1'S, 2'S)-2-(karboksycyklopropylo)glicyna (L-CCG-I), hamowały... more
... mGluR (2S,1'R, 2'R,3'R)-2-(2,3-dikarboksycyklopropylo)glicyna (DCG-IV), jak również 4C3HPG, oraz (2S,1'S, 2'S)-2-(karboksycyklopropylo)glicyna (L-CCG-I), hamowały ekscytotokstyczne działanie NMDA w tym modelu [21]. Neuroprotekcja była obserwo-wana kiedy związki ...
The existence of multiple metabotropic receptors for excitatory amino acids is firmly established by recent cloning experiments. Several subtypes of those receptors are coupled to adenylate cyclase.... more
The existence of multiple metabotropic receptors for excitatory amino acids is firmly established by recent cloning experiments. Several subtypes of those receptors are coupled to adenylate cyclase. (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R)-ACPD) is a selective agonist for metabotropic glutamate receptors, it influences cyclic AMP accumulation in brain and is able to enhance the effect of other substances which stimulate cyclic AMP accumulation. Here we present data showing that (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid enhanced the action of noradrenaline on cyclic AMP accumulation in rat brain cortical slices (EC50 40 microM). On the contrary, it inhibited the action of noradrenaline in primary glial cell cultures (EC50 50 microM), being without any effect on noradrenaline-induced cyclic AMP accumulation in primary neuronal cell cultures. The differences may reflect stimulation of different types of metabotropic glutamate receptors in various preparations f...
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Metabotropic glutamate receptors and muscarinic M receptors have been proposed as novel targets for various brain disorders, including schizophrenia. Both receptors are coupled to G proteins and are expressed in brain circuits that are... more
Metabotropic glutamate receptors and muscarinic M receptors have been proposed as novel targets for various brain disorders, including schizophrenia. Both receptors are coupled to G proteins and are expressed in brain circuits that are important in schizophrenia. Therefore, their mutual activation may be an effective treatment and allow minimizing the doses of ligands required for optimal activity. In the present studies, subactive doses of mGlu and M activators (LSP4-2022 and VU152100, respectively) were administered to investigate the mutual interaction between mGlu and M receptors in animal models of schizophrenia. The behavioral tests used were MK-801-induced hyperactivity, (±)-2.5-dimethoxy-4-iodoamphetamine hydrochloride (DOI)-induced head twitches, the modified forced swim test, and MK-801-induced disruptions of social interactions and novel object recognition. DOI-induced spontaneous excitatory postsynaptic currents (sEPSCs) in brain slices and positron emission tomography (...
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Recent preclinical studies point to muscarinic and GABA receptors as novel therapeutic targets for the treatment of schizophrenia. This study was aimed to assess the role of muscarinic and GABA receptor interactions in animal models of... more
Recent preclinical studies point to muscarinic and GABA receptors as novel therapeutic targets for the treatment of schizophrenia. This study was aimed to assess the role of muscarinic and GABA receptor interactions in animal models of schizophrenia, using positive allosteric modulators (PAMs) of GABA receptor (GS39783), muscarinic M (VU0152100) and M (VU0238429) receptor, and partial allosteric agonist of M receptor (VU0357017). DOI-induced head twitches, social interaction and novel object recognition tests were used as the models of schizophrenia. Analyses of DOI-induced increases in sEPSCs (spontaneous excitatory postsynaptic currents) were performed as complementary experiments to the DOI-induced head twitch studies. Haloperidol-induced catalepsy and the rotarod test were used to examine the adverse effects of the drugs. All three activators of muscarinic receptors were active in DOI-induced head twitches. When administered together with GS39783 in subeffective doses, only the ...
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There is conflicting evidence on the impact of biologic treatment on the rate of complications and surgeries in Crohn's disease (CD). We aimed to assess real-world consequences of biologic treatment of CD. All adult patients with CD... more
There is conflicting evidence on the impact of biologic treatment on the rate of complications and surgeries in Crohn's disease (CD). We aimed to assess real-world consequences of biologic treatment of CD. All adult patients with CD treated with infliximab and adalimumab in the years 2012-2014 were identified from the database of the National Health Fund in Poland. Mixed models were used to assess the impact of biologics on medical resource utilization by comparing the periods before and after the first use of biologics (pre-index vs. post-index). The additional analyses including quintile of total exposure to biologic treatment were performed. Data on 1393 patients (age, 31.9 years; males, 52.6%) were analyzed over a median of 1064 days (range: 71, 1148). During the post-index period, patients received from one to four treatments with biologic agents (maximum allowed period of 12 months per treatment). We observed a reduction in the rates of surgeries (by 27%, = 0.001), hospita...
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The aim was to evaluate the cost-effectiveness of Crohn's disease (CD) treatment with vedolizumab and ustekinumab after failure of therapy with tumor necrosis factor-α antagonists (anti-TNFs). The Markov model incorporated the... more
The aim was to evaluate the cost-effectiveness of Crohn's disease (CD) treatment with vedolizumab and ustekinumab after failure of therapy with tumor necrosis factor-α antagonists (anti-TNFs). The Markov model incorporated the lifetime horizon, synthesis-based estimates of biologics' efficacy in relation to anti-TNF exposure, and administration of biologics reflecting clinical practice (e.g., sequence of biologics, retreatment, 12-month treatment). The utilities, non-medical costs and indirect costs were derived from a study of 200 adult patients with CD, while the healthcare costs were from a study of 1393 adults with CD who used biologics in Poland. The quality-adjusted life years (QALYs) and costs (the societal perspective) were discounted with the annual rates of 3.5 and 5%, respectively. The addition of vedolizumab (ustekinumab) to the sequence of available anti-TNFs (after first-line infliximab or after second-line adalimumab) led to a gain of 0.364 (0.349) QALYs at an...
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The aim of this study was to review reimbursement environment as well as pricing and reimbursement requirements for drugs in selected Central and Eastern Europe (CEE) countries.A questionnaire-based survey was performed in the period from... more
The aim of this study was to review reimbursement environment as well as pricing and reimbursement requirements for drugs in selected Central and Eastern Europe (CEE) countries.A questionnaire-based survey was performed in the period from November 2016 to March 2017 among experts involved in reimbursement matters from CEE countries: Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Slovakia, and Romania. A review of requirements for reimbursement and implications of Health Technology Assessment (HTA) was performed to compare the issues in above-mentioned countries. For each specified country, data for reimbursement costs, total pharmaceutical budget, and total public health care budget in the years 2014 and 2015 were also collected. Questionnaires were distributed via emails and feedback data were obtained in the same way. Additional questions, if any, were also submitted to respondents by email. Pricing and reimbursement data were valid for March 2017....
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Some clinical studies indicate that scopolamine may induce a rapid antidepressant effect. Although scopolamine is a muscarinic antagonist, it seems that not only cholinergic but also glutamatergic and GABAergic systems might be involved... more
Some clinical studies indicate that scopolamine may induce a rapid antidepressant effect. Although scopolamine is a muscarinic antagonist, it seems that not only cholinergic but also glutamatergic and GABAergic systems might be involved in the mechanism of its antidepressant activity in animal models of depression. Here, we present a set of behavioral data aimed at investigating the role of monoaminergic system activity in the mechanism of the antidepressant-like action of scopolamine in an animal model based on behavioral despair, namely, the tail suspension test (TST). It was found that AMPT induced a partial reduction in the antidepressant-like effect of scopolamine (0.3mg/kg) in the TST in C57BL/6 mice and that the effect of scopolamine was comparable to the effect of reboxetine (10mg/kg), which was used in this study as a reference drug. The attenuated antidepressant-like effect of scopolamine in AMPT-treated mice was observed in both its immediate (30min after administration) ...
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Clinical studies have shown that the muscarinic receptor antagonist scopolamine induces a potent and rapid antidepressant effect relative to conventional antidepressants. However, potential undesirable effects, including memory... more
Clinical studies have shown that the muscarinic receptor antagonist scopolamine induces a potent and rapid antidepressant effect relative to conventional antidepressants. However, potential undesirable effects, including memory impairment, partially limit the use of scopolamine in psychiatry. In the present study, we propose to overcome these limitations and enhance the therapeutic effects of scopolamine via administration in combination with the group II metabotropic glutamate (mGlu) receptor antagonist, LY341495. Joint administration of sub-effective doses of scopolamine (0.03 or 0.1 mg/kg, i.p.) with a sub-effective dose of LY341495 (0.1 mg/kg, i.p.) induced a profound antidepressant effect in the tail suspension test (TST) and in the forced swim test (FST) in mice. This drug combination did not impair memory, as measured using the Morris water maze (MWM), and did not influence the locomotor activity of mice. Furthermore, we found that an AMPA receptor antagonist, NBQX (10 mg/kg)...
Research Interests: Psychology, Neuropharmacology, Prefrontal Cortex, Serotonin, Mice, and 11 moreAnimals, Metabotropic Glutamate Receptors, Male, Depressive Disorder, Amino Acids, Maze Learning, Neurosciences, Motor activity, Pharmacology and pharmaceutical sciences, Antidepressive agents, and Scopolamine hydrobromide
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The appropriate access to public information is very important for healthcare system stakeholders. The goal of this study was to examine how the execution of the formally existing right to public information on the HTA-based... more
The appropriate access to public information is very important for healthcare system stakeholders. The goal of this study was to examine how the execution of the formally existing right to public information on the HTA-based recommendations on reimbursement of new health technologies from public funds has been changing in Poland. All recommendations published within two predefined equal periods of time between 2013 and 2015 were analyzed. The gathered data was subjected to statistical analysis. The frequency and intensity of censoring the published HTA-based recommendations on the pharmaceutical reimbursement has diminished. The text readability and clarity of message has improved, although the degree of decisiveness of the recommendations has dropped. The positive changes in the public communication policy should be continued. The transparency of the HTA-based recommendations should be increased further in some areas in the future.
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Crohn disease (CD) is an inflammatory bowel disease which occurs especially in developed countries of Western Europe and North America. The aim of the study was to compare the safety profile of biologic drugs in patients with CD. A... more
Crohn disease (CD) is an inflammatory bowel disease which occurs especially in developed countries of Western Europe and North America. The aim of the study was to compare the safety profile of biologic drugs in patients with CD. A systematic literature search was performed using PubMed, Embase, and CENTRAL databases, until April 27, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, vedolizumab, certolizumab pegol, and ustekinumab) with one another or with placebo in patients with CD. The network meta-analysis (NMA) was conducted for an induction phase (6-10 weeks) and maintenance phase (52-56 weeks) with a Bayesian hierarchical random effects model in the ADDIS(®) software. The PROSPERO registration number was CRD42016032606. Ten RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, vedolizumab, certolizumab pegol, and ustekinumab, and in the case of the maintenance phase-of infliximab, adalimumab, and vedolizumab. There were no significant differences in the rate of adverse events in patients treated with biologics. Statistical analysis revealed that vedolizumab had the greatest probability of being the safest treatment in most endpoints in the induction phase and adalimumab-in the maintenance phase. No significant differences between the biologics in the relative safety profile analysis were observed. Further studies are needed to confirm our findings, including head-to-head comparisons between the analyzed biologics.
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Biologic drugs are used in innovative therapies for the management of inflammatory bowel diseases (IBDs). The aim of this study was to compare the safety profile of biologic drugs in patients with IBD. A systematic literature search was... more
Biologic drugs are used in innovative therapies for the management of inflammatory bowel diseases (IBDs). The aim of this study was to compare the safety profile of biologic drugs in patients with IBD. A systematic literature search was performed using PubMed, Embase, and CENTRAL databases, up to 22 August 2016. We included randomized, placebo-controlled, or head-to-head clinical trials that compared the safety of different biologics in patients with IBDs. Two reviewers independently conducted the search and selection of studies and rated each trial's risk of bias. The network meta-analysis (NMA) was conducted for a mid-term (20-30 weeks) and long-term (≥52 weeks) follow-up with a Bayesian hierarchical random effects model using the ADDIS(®) software. The PROSPERO registration number was CRD42015029884. Sixteen randomized controlled trials were included in the systematic review with NMA. In the case of the mid-term follow-up, it was possible to conduct the NMA for assessing the relative safety profile of certolizumab pegol and infliximab, and in the case of the long-term follow-up, of infliximab, adalimumab, golimumab, and vedolizumab. There were no significant differences in the rate of adverse events in patients treated with all analyzed biologic drugs for IBD. The analysis of probability for being the safest treatment showed that infliximab was the best option in most analyzed endpoints both in mid-term and in long-term follow-ups. We showed no significant differences in the relative safety profile of the analyzed biologic drugs. Further studies are needed to confirm our findings, including head-to-head comparisons between these drugs.
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LSP4-2022 is a novel, orthosteric agonist of mGlu4 receptor that induces antipsychotic-like activity in animal studies. In the present study, the involvement of 5-HT1A receptors in LSP4-2022-induced antipsychotic actions and the... more
LSP4-2022 is a novel, orthosteric agonist of mGlu4 receptor that induces antipsychotic-like activity in animal studies. In the present study, the involvement of 5-HT1A receptors in LSP4-2022-induced antipsychotic actions and the neurochemical background of that interaction were investigated. In several behavioral tests the actions of effective doses of the compound (0.5-2 mg/kg) were antagonized via the administration of the 5-HT1A antagonist WAY100635 (0.1 mg/kg). The co-administration of sub-effective dose of the 5-HT1A agonist (R)-(S)-8-OH+DPAT (0.01 mg/kg) intensified the activity of ineffective dose of LSP4-2022, having no influence on the efficacy of the active dose. The co-administration of effective doses of both compounds did not intensify each other's action. In the microdialysis in vivo tests, MK-801 (0.6 mg/kg) induced an enhancement of the release of dopamine, serotonin, glutamate and GABA in the prefrontal cortex. Administration of LSP4-2022 (2 mg/kg) abolished thi...
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In large, mostly English-speaking countries, where the "critical mass" of scientists working in different subfields of... more
In large, mostly English-speaking countries, where the "critical mass" of scientists working in different subfields of science is achieved, the peer review system may be sufficient to assess the quality of scientific research. However, in smaller countries, outside the Anglo-American circle, it is important to introduce different systems to identify research of high quality. In Poland, a parametric system for assessing the quality of research has been introduced. It was largely based on the impact factor of scientific journals. While the use of this indicator to assess research quality is highly questionable, the implementation of the system in the Polish reality is even worse. Therefore it is important to change and improve the system currently used by the Ministry of Science and Higher Education to both evaluate and, more importantly, finance science in Poland. Here, a system based on three factors, i.e. the impact factor, the institutional h-index, and the institutional number of citations, is proposed. The scientific quality of institutions in Division VI: Medical Sciences of the Polish Academy of Sciences were evaluated and the results were compared with the existing system. Moreover, a method to identify high-quality researchers and institutions at the national level based on the quantity of highly cited papers is shown. Additionally, an attempt to identify the highest quality Polish research on an international level is proposed. This is based on the number of individual citations, the individual h-index, the number of publications, and the priority of the discovery.
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The increasing prevalence of Crohn disease (CD) underscores the need to identify new effective drugs, which is particularly important for patients who do not respond or do not tolerate standard biologic therapies. The purpose of this... more
The increasing prevalence of Crohn disease (CD) underscores the need to identify new effective drugs, which is particularly important for patients who do not respond or do not tolerate standard biologic therapies. The purpose of this analysis was to compare the efficacy and safety of vedolizumab and certolizumab pegol in patients with active moderate to severe CD. This analysis was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic literature search of Medline (PubMed), Embase, and the Cochrane Library was conducted through March 5, 2016. Studies included were randomized controlled trials (RCTs) that enrolled patients treated for CD with vedolizumab or certolizumab pegol. All studies were critically appraised; indirect comparison was performed with the Bucher method. Eight RCTs were identified, and four were homogeneous enough to be included in the indirect comparison of the induction phase of treatment. No statistically significant differences were found in clinical response (relative risk [RR] 1.23, 95% confidence interval [CI] 0.81-1.88) or remission (RR 1.35, 95% CI 0.89-2.07) between vedolizumab and certolizumab pegol in the overall population. Similar nonstatistically significant differences in response and remission were noted in a subgroup analysis of anti-tumor necrosis factor-naive patients (RR 1.10, 95% CI 0.72-1.66 and RR 1.98, 95% CI 0.95-4.11, respectively). In addition, there were no statistically significant differences in safety profiles. This indirect comparison analysis demonstrated no statistically significant differences in efficacy and safety between vedolizumab and certolizumab pegol.
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Classic antidepressants that modulate monoaminergic systems are not sufficiently effective and require long systematic application. Recent studies suggest that substances that modulate glutamatergic system may produce an antidepressant... more
Classic antidepressants that modulate monoaminergic systems are not sufficiently effective and require long systematic application. Recent studies suggest that substances that modulate glutamatergic system may produce an antidepressant effect which is not only faster but also more sustained. In this paper, the authors summarize the results of studies on antidepressant action of ketamine in patients with severe refractory depression, which have demonstrated high efficacy in a very short time after a single dose. Due to the adverse effects of ketamine that substantially exclude it from the daily use by patients, efforts have been made to find other NMDA receptor antagonists, which could mimic the therapeutic effect of ketamine but without the side effects. Intensive studies to elucidate ketamine's mechanism of antidepressant action have also been conducted. Herein, the results of research showing that metabotropic glutamate (mGlu) receptors could be the target of novel antidepressants are also presented. The intensive preclinical and clinical research on NMDA and mGlu receptor ligands, which is currently going on, could contribute to the awaited breakthrough in the field of novel antidepressant drug discovery. This line of research may also lead to a new understanding of the biological basis of depression.
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Using the conflict drinking Vogel test in rats as a model we examined the anxiolytic-like activity of (RS)-alpha-methylserine-O-phosphate (MSOP) and (RS)-alpha-methylserine-O-phosphate-monophenyl ester (MSOPPE), the antagonists of group... more
Using the conflict drinking Vogel test in rats as a model we examined the anxiolytic-like activity of (RS)-alpha-methylserine-O-phosphate (MSOP) and (RS)-alpha-methylserine-O-phosphate-monophenyl ester (MSOPPE), the antagonists of group III and II of mGluR, respectively, after their intrahippocampal administration. The results indicated that MSOP produced a dose dependent anticonflict effect in rats.
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Depression and anxiety are psychiatric disorders with high morbidity and comorbidity. Because of multiple adverse effects of existing drugs and a low efficacy, therapy for a substantial number of patients is unsatisfactory. It is widely... more
Depression and anxiety are psychiatric disorders with high morbidity and comorbidity. Because of multiple adverse effects of existing drugs and a low efficacy, therapy for a substantial number of patients is unsatisfactory. It is widely accepted that gamma-aminobutyric acid (GABA) is the primary inhibitory transmitter substance in the mammalian central nervous system. Data are accumulating that the recently cloned GABAB receptors might become a target for the development of new antidepressant and/or anxiolytic drugs. The existing data support the hypothesis that agonists and particularly positive modulators of GABAB receptors (but not GABAB receptor antagonists) may be anxiolytic drugs in the future. The experiments demonstrate that the most consistent finding following chronic administration of antidepressants is an increase in GABAB receptor function, with or without a change in receptor binding or subunit expression. Data are accumulating in preclinical studies that show that antagonists (but not agonists) of GABAB receptors may have antidepressant effects.
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The effects of zinc, the NMDA receptor inhibitor, were studied in the forced swimming (Porsolt's) test in mice. Zinc (ZnSO4) at a dose of 30 mg/kg (but not at a dose of 10 mg/kg), similarly to imipramine (30 mg/kg), reduced the... more
The effects of zinc, the NMDA receptor inhibitor, were studied in the forced swimming (Porsolt's) test in mice. Zinc (ZnSO4) at a dose of 30 mg/kg (but not at a dose of 10 mg/kg), similarly to imipramine (30 mg/kg), reduced the immobility time in that test. Moreover, zinc at both doses reduced the locomotor activity. The obtained results indicate that zinc induces an antidepressant-like effect in the forced swimming test. Since zinc reduces the locomotor activity, this antidepressant-like effect is not related to the alteration of general activity.
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To assess the cost-effectiveness of infliximab with standard care (e.g., azathioprine, prednisolone, mesalazine, and 6-mercaptopurine) versus standard care alone for induction and maintenance treatment of patients with ulcerative colitis... more
To assess the cost-effectiveness of infliximab with standard care (e.g., azathioprine, prednisolone, mesalazine, and 6-mercaptopurine) versus standard care alone for induction and maintenance treatment of patients with ulcerative colitis in Poland. Cost-utility decision analytic model. A Markov model was used to estimate the expected costs and effects of infliximab/standard care and standard care alone. For each treatment option, costs and quality-adjusted life years (QALYs) were calculated to estimate the incremental cost-utility ratio. The target population consisted of a hypothetical cohort of adult patients with moderately to severely active ulcerative colitis who had an inadequate response to standard treatment, including corticosteroids and 6-mercaptopurine or azathioprine, or who were intolerant to or had medical contraindications to such therapies. The analysis was performed from the perspective of the Polish public payer over a 30-year time horizon. The clinical parameters ...
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We examined the anxiolytic-like activity of2-methyl-6-(phenylethynyl)-pyridine (MPEP) using the conflict drinking Vogel test in rats as a model. MPEP is a selective and brain-penetrable mGlu5 receptor antagonist, the most potent compound... more
We examined the anxiolytic-like activity of2-methyl-6-(phenylethynyl)-pyridine (MPEP) using the conflict drinking Vogel test in rats as a model. MPEP is a selective and brain-penetrable mGlu5 receptor antagonist, the most potent compound described so far. The results indicate that MPEP produced a dose-dependent anticonflict effect in rats. These data suggest that selective mGlu5 receptor antagonists may become a new class of anxiolytics.
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Recent literature data and the results of our earlier pharmacological studies, have provided evidence that antagonists of group I metabotropic glutamate receptors (mGluRs) and agonists of group II mGluRs show anxiolytic-like properties in... more
Recent literature data and the results of our earlier pharmacological studies, have provided evidence that antagonists of group I metabotropic glutamate receptors (mGluRs) and agonists of group II mGluRs show anxiolytic-like properties in preclinical and clinical studies. Out of all glutamate receptors, the role of group III mGluRs in anxiety-like states is the least investigated because of the lack of specific pharmacological tools, moreover all group III receptor ligands synthesized so far are not systemically active, so they have to be administered centrally. In the present study, we investigated the anxiolytic-like activity of group III mGlu receptor ligands including a nonselective group III mGlu receptor agonist (1S,3R,4S)-1-aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-I), group III mGlu receptor antagonist, (RS)-alpha -cyclopropyl-4-phosphonophenylglycine (CPPG) and a positive allosteric modulator of mGluR4 (-)-N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC). The Vogel conflict drinking test in rats was used to test the anxiolytic-like effects. The hippocampus was chosen as a site of the injection of drugs, as this brain regions is involved in the regulation of anxiety-related behavior. Intrahippocampal injections (CA1 region of the hippocampus) of PHCCC (12 nmol) but not of CPPG (75 nmol ) produced an anxiolytic-like response, moreover, the effect of PHCCC was totally blocked by CPPG. The anxiolytic-like effects of ACPT-I (7.5 nmol) or PHCCC (12 nmol) were significantly attenuated by flumazenil (10 mg/kg), indicating an involvement of GABAergic system in the anxiolytic-like response.
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Research Interests: Psychology, Neuropharmacology, Animals, Metabotropic Glutamate Receptors, Male, and 13 moreOpen Field, Electromyography, Haloperidol, Rats, Pyridines, Wistar Rats, Locomotor Activity, Neurosciences, Glutamate Receptor, Motor activity, Antipsychotic agents, Catalepsy, and Pharmacology and pharmaceutical sciences
Over-the-counter (OTC) medicines and dietary supplements are increasingly popular in Poland, potentially improving but also potentially posing a threat to public health. The study goal is to characterize and assess behaviors related to... more
Over-the-counter (OTC) medicines and dietary supplements are increasingly popular in Poland, potentially improving but also potentially posing a threat to public health. The study goal is to characterize and assess behaviors related to use of OTC medicines and dietary supplements among Polish university students. A questionnaire-based survey was performed with students divided into groups (gender, subjects studied, period of studies). The majority of students declared using the products, significantly more females and younger students in their early years. Females tended to be more attentive to product information. Students with a background in biological or medical sciences were also more attentive and less influenced by advertising. The authors present that the differences between the defined groups of students should be utilized in tailored educational activities, aiming to rationalize high consumption of OTC medicines and dietary supplements. Targeting other, especially low-socioeconomic and less-educated, groups should follow.
Research Interests:
The aim of our study was to investigate the level of metabotropic glutamate receptors (mGluRs) in the brains of rats after chronic mild stress. Using Western blotting procedure we showed that the level of mGluR5 receptor protein was... more
The aim of our study was to investigate the level of metabotropic glutamate receptors (mGluRs) in the brains of rats after chronic mild stress. Using Western blotting procedure we showed that the level of mGluR5 receptor protein was increased in CA1 and decreased in CA3 region of the hippocampus. Our results indicate that mGluR5 can possibly be engaged in the mechanism of depression.