Srovnani vlivu systemove premedikace, akutniho podani a intracerebralni aplikace D2 antagonisty raclopridu na metabolickou aktivitu vybraných isoforem CYP450 u potkana.
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The study describes the influence of methamphetamine and raclopride administered separately and together on the metabolic activity of rat hepatal 2D2 isoenzyme.
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Memantine is an inhibitor of CYP2D2 in rats in both experimental models used and moreover the inhibition of fluoxetine was modulated by memantine administration.
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Pro urceni metabolickeho fenotypu 2D6 formy cytochromu P450 (CYP2D6) se dlouhodobě použiva poměru koncentraci dextrometorfanu/dextrorfanu (MRDEM/DOR) v moci pacientů sbirane 8 hod po podani modeloveho substratu dextrometorfanu (DM).... more
Pro urceni metabolickeho fenotypu 2D6 formy cytochromu P450 (CYP2D6) se dlouhodobě použiva poměru koncentraci dextrometorfanu/dextrorfanu (MRDEM/DOR) v moci pacientů sbirane 8 hod po podani modeloveho substratu dextrometorfanu (DM). Hodnota MRDEM/DOR = 0,3 je považovana za hranici oddělujici extenzivni (EM) a pomale (PM) metabolizatory. Sběr moci po 8 hod vsak býva u psychiatrických pacientů problematický. Cilem prace bylo ověřit korelaci mezi MRDEM/DOR v moci (0-8 h) a seru (3 h) po podani DM.MRDEM/DOR v seru a moci velmi silně koreluje (r2 = 0,919). MRDEM/DOR jsou vyssi v seru než v moci (median MRDEM/DOR 3-h serum = 0,0156, median MRDEM/DOR 8-h moc = 0,0096). Predikce metabolicke aktivity a fenotypu CYP2D6 stanovenim MRDEM/DOR ze sera je diky nalezene silne korelaci mezi MRDEM/DOR v moci a seru spolehliva. Pro stanoveni hranicni hodnoty MRDEM/DOR v seru sloužici k jasnemu odděleni EM a PM je třeba nasbirat vice dat, předevsim ze skupiny PM. Jednodussi způsob stanoveni metabolicke aktivity CYP2D6 pomůže individualizovat farmakoterapii u psychiatrických pacientů.
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ABSTRACT Cannabinoid CB1 receptor stimulation by an agonist cross-sensitized to metamphetamine, while blocking of the CB1 receptor with an antagonist during the sensitizing phase with methamphetamine suppressed this phenomenon. The CB2... more
ABSTRACT Cannabinoid CB1 receptor stimulation by an agonist cross-sensitized to metamphetamine, while blocking of the CB1 receptor with an antagonist during the sensitizing phase with methamphetamine suppressed this phenomenon. The CB2 receptor agonist eliciting in our model of aggressivity behavioural effects did not cause cross-sensitization to methamphetamine.
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Memantine, an antagonist of NMDA, 5HT3 and some neuronal nicotinic receptors, is used in the treatment of Alzheimer's disease. There are also many other indications for memantine, which are being tested nowadays including depression,... more
Memantine, an antagonist of NMDA, 5HT3 and some neuronal nicotinic receptors, is used in the treatment of Alzheimer's disease. There are also many other indications for memantine, which are being tested nowadays including depression, opioid dependence, neuropathic pain and others. The aim of our study was to evaluate the influence of memantine on the activity of cytochrome P450 (CYP450). CYP450 is one of the major biotransforming systems in organism and consists of many isoenzymes. The importance of CYP450 in clinical practice is that the huge numbers of drugs are substrates for this enzyme. We have focused on 2D2 rat isoenzyme (equivalent for human 2D6), because of its relation to the metabolism of many psychoactive drugs and clinical possibilities of their co-administration with memantine. The model of isolated perfused rat liver and dextrometorphan specific marker for determination of CYP2D6 activity were used. Memantine was administered to male rats intraperitoneally at the dose of 5 mg/kg/day for 10 days prior to the liver isolation and perfusion. Metabolic transformation of dextrometorphan via CYP2D2 was inhibited in memantine-treated animals. We suggest that a higher risk of adverse effects should be taken in account when memantine is co-administered with drugs metabolized through CYP2D6 pathway.
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Podobně jako v připadě metamfetaminu, opakovana aplikace extaze vyvolala u mysi v testu otevřeneho pole rozvoj behavioralni senzitizace. Opakovana premedikace agonistou CB1 receptoru metanandamidem vedla k rozvoji zkřižene senzitizace k... more
Podobně jako v připadě metamfetaminu, opakovana aplikace extaze vyvolala u mysi v testu otevřeneho pole rozvoj behavioralni senzitizace. Opakovana premedikace agonistou CB1 receptoru metanandamidem vedla k rozvoji zkřižene senzitizace k ucinkům extaze a naopak opakovana aplikace antagonisty CB1 receptoru AM 251+MDMA tento fenomen potlacila.
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The study is iamed on the influence of intracerebral administration of substance O-2545 HCl on the metabolic activity of CYP450 in rat liver.
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Opakovana aplikace MDMA vyvolala u mysi v testu otevřeneho pole rozvoj i expresi senzitizace. Opakovana premedikace agonistou CB1 receptoru vedla ke zkřižene senzitizaci k ucinkům provokujici davky MDMA a naopak opakovana aplikace... more
Opakovana aplikace MDMA vyvolala u mysi v testu otevřeneho pole rozvoj i expresi senzitizace. Opakovana premedikace agonistou CB1 receptoru vedla ke zkřižene senzitizaci k ucinkům provokujici davky MDMA a naopak opakovana aplikace antagonisty CB1 receptoru+MDMA tento fenomen potlacila. Nepodařilo se potvrdit hypotezu, že by opakovana aplikace MDMA senzitizovala k antiagresivnimu působeni v modelu agonistickeho chovani.
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Ziskane výsledky prokazaly, že pohlavni rozdily v behavioralnich odpovědich mysi na MDMA jsou podminěny vlivem přirozených estrogenů na chovani samic, neboť u kastrovaných samic bez hormonalni substituce bylo zaznamenano podobne chovani... more
Ziskane výsledky prokazaly, že pohlavni rozdily v behavioralnich odpovědich mysi na MDMA jsou podminěny vlivem přirozených estrogenů na chovani samic, neboť u kastrovaných samic bez hormonalni substituce bylo zaznamenano podobne chovani jako u samců, zatimco behavioralni odpověď samic s hormonalni substituci odpovidala chovani samicich skupin v předchozich experimentech.
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Sledovani změn metabolicke aktivity vybraných hepatalnich izoenzymů CYP450, po blokadě dopaminových D2 receptorů raklopridem.
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V praci byla sledovana interakce mezi metamfetaminem a ethanolem na preklinicke urovni. Metamfetamin urychluje biotransformaci akutni davky etanolu v použitem modelu a casovem schematu.
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The study sumarizes the knowledge of the correlation of metabolic phenotype and genotype of CYP2D6 with the therapeutical response in first episode- schizphrenic patients treated with risperidone.
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Sledovali sme vplyv LI160 na leukocytarnu fagocytozu v modeli olfaktorickej bulbektomie, ktorý sa použiva ku skriningu antidepresivnych ucinkov. Bulbektomia u potkanov navodzuje subor charakteristických zmien, ktore selektivne reaguju na... more
Sledovali sme vplyv LI160 na leukocytarnu fagocytozu v modeli olfaktorickej bulbektomie, ktorý sa použiva ku skriningu antidepresivnych ucinkov. Bulbektomia u potkanov navodzuje subor charakteristických zmien, ktore selektivne reaguju na chronicke podavanie antidepresiv. Ucinnosť LI160 sme overili testom otvoreneho poľa, z imunitných zmien sme hodnotili leukocytarnu fagocytozu, ktora odraža bunkovu imunitnu funkciu. U potkanov bola prevedena ablacia obidvoch olfaktorických bulbov. Cuchový organ kontrolnej skupiny zvierat zostal intaktný. Obidvom skupinam bol 10 dni intraperitonealne aplikovaný fyziologický roztok (2 ml/kg/deň) alebo standardizovaný extrakt LI160 z Hypericum perforatum (100 mg/kg/deň). Nasledne bol prevedený desaťminutový zaznam lokomotorickej aktivity a odobrata krv na chemiluminometricke stanovenie leukocytarnej fagocytozy. LI160 inhiboval hyperlokomociu navodenu bulbektomiou, bez ovplyvnenia motoriky kontrolných potkanov, co svedci pre antidepresivny ucinok v použitom modele depresie. U bulbektomovaných potkanov bola znižena leukocytarna fagocytoza. LI160 stimuloval tuto imunitnu funkciu u obidvoch skupin zvierat. Imunostimulacný ucinok LI160 može mať význam v klinike pri dlhodobom podavani pripravkov z Hypericum perforatum.
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Research Interests: Biology and Peripheral
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Byl sledovan vliv intracerebralni aplikace smiseneho CB1/CB2 agonisty O2545 na metabolickou aktivitu vybraných izoenzymů CYP450 v jatrech. Výsledky dokladaji na koncentraci zavislý efekt testovane latky.
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Cilem experimentu bylo popsat vliv standardizovaneho extraktu LI 160 na metabolickou aktivitu CYP2D1/2 na modelu izolovaných perfundovaných jater.
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On selecting a constituent part of MU the" Overview of publishing activities" page will be displayed with information relevant to the selected constituent part. The" Overview of publishing activities" page is not... more
On selecting a constituent part of MU the" Overview of publishing activities" page will be displayed with information relevant to the selected constituent part. The" Overview of publishing activities" page is not available for non-activated items.
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Pedkladana prace pinasi souhrnn nahled do problematiky metamfetaminove zavislosti a pedevsim popisuje vliv kombinovaneho podani metamfetaminu se serotonergn psobicim antidepresivem fluoxetinem ve vlastnich experimentech, a to ve dvou... more
Pedkladana prace pinasi souhrnn nahled do problematiky metamfetaminove zavislosti a pedevsim popisuje vliv kombinovaneho podani metamfetaminu se serotonergn psobicim antidepresivem fluoxetinem ve vlastnich experimentech, a to ve dvou zviecich modelech, behavioralnim a farmakokinetickem. V nich byl studovan vliv fluoxetinu na pijem metamfetaminu v potkanim modelu zavislosti (i. v. drug self-administration) a na zmny metabolicke aktivity vybraných izoenzym cytochromu P450 v modelu izolovaných perfundovaných potkanich jater. Po aplikaci fluoxetinu bylo popsano sniženi pijmu metamfetaminu u zavislých potkan a anti-biodegradani efekt na metamfetaminem psobenou inhibici oxidani aktivity CYP2C6, CYP2D2 a CYP3A1/2. Vlastni výsledky jsou prezentovany v konfrontaci s korespondujicimi literarnimi udaji. Cilem je upozornit na dalsi možnou farmakologickou intervenci pi leb piznak zavislosti na metamfetaminu a pro usnadnni abstinence.
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The aim of this work was to elucidate if CYP2D6 phenotyping by evaluation of molar dextromethorphan to dextrorphan metabolic ratio (MRDEM/DOR) in serum has the usability and reliability as the assessment of MRDEM/DOR in urine. We measured... more
The aim of this work was to elucidate if CYP2D6 phenotyping by evaluation of molar dextromethorphan to dextrorphan metabolic ratio (MRDEM/DOR) in serum has the usability and reliability as the assessment of MRDEM/DOR in urine. We measured MRDEM/DOR in serum and CYP2D6 genotype in 51 drug-naive patients and investigated cut-off value for discrimination of poor metabolizers from extensive and intermediate ones. The correlation of serum MRDEM/DOR with urine MRDEM/DOR in 30 healthy volunteers was analysed in parallel.
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Cilem experimentu bylo popsat vliv standardizovaneho extraktu LI 160 na metabolickou aktivitu CYP2D1/2 na modelu izolovaných perfundovaných jater.
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Various psychostimulant drugs induce after their repeated administration a significant increase in behavioural responses, phenomenon known as behavioural sensitization. In our recent studies we demonstrated development of this phenomenon... more
Various psychostimulant drugs induce after their repeated administration a significant increase in behavioural responses, phenomenon known as behavioural sensitization. In our recent studies we demonstrated development of this phenomenon after repeated administration of methamphetamine (Met) and its expression following Met challenge dose after the withdrawal lasting 6 days. Furthermore, pretreatment with CB1 receptor agonist methanandamide elicited behavioural cross-sensitization to Met stimulatory effects. By analogy, we decided to test a possible cross-sensitization to Met with another widely abused substance - MDMA (ecstasy), and vice versa with Met repeated pretreatment to MDMA effects.
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CYP2D6 plays a pivot role in metabolism of xenobiotics, especially psychotropic drugs. Predicting its metabolic activity in patients may help to personalize pharmacotherapy.Eight-hour urinary ratio of dextromethorphan/dextrorphan molar... more
CYP2D6 plays a pivot role in metabolism of xenobiotics, especially psychotropic drugs. Predicting its metabolic activity in patients may help to personalize pharmacotherapy.Eight-hour urinary ratio of dextromethorphan/dextrorphan molar concentrations (MRDEM/DOR) serves as a measure of CYP2D6 activity with 0.3 as a cut-off value separating poor (PM) and extensive metabolizers (EM) (1). Unfortunately, collecting of urine for 8 hours may be difficult in psychiatric patients. The assessment of MRDEM/DOR in serum is less used since correlation with urine MRDEM/DOR and cut-off value in serum is not well established. The aim of this study was to find out correlation between MRDEM/DOR in serum and urine and to identify cut-off value separating EM from PM and possibly also EM from intermediate metabolizers (IM) and IM from PM. Correlation was done in 28 healthy volunteers, blood samples were withdrawn 3 hours after ingestion of 30 mg of dextromethorphan hydrobromide and urine was collected f...
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On selecting a constituent part of MU the" Overview of publishing activities" page will be displayed with information relevant to the selected constituent part. The" Overview of publishing activities" page is not... more
On selecting a constituent part of MU the" Overview of publishing activities" page will be displayed with information relevant to the selected constituent part. The" Overview of publishing activities" page is not available for non-activated items.
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Study aimed on the influence of methanadamide intraperitoneal pretreatment on rat CYP 1A2 and 2C6 activity in liver.
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Kniha přinasi přehled hlavnich ucinných latek v rostlině konopi, ktere maji terapeutický potencial, zabýva se jejich farmakokinetikou a mechanismy ucinku. Zaměřuje se na možne terapeuticky prospěsne ucinky kanabinoidů při lecbě nenadorove... more
Kniha přinasi přehled hlavnich ucinných latek v rostlině konopi, ktere maji terapeutický potencial, zabýva se jejich farmakokinetikou a mechanismy ucinku. Zaměřuje se na možne terapeuticky prospěsne ucinky kanabinoidů při lecbě nenadorove i nadorove bolesti, spastických stavů a zvraceni. Jedna z kapitol je zaměřena na pravni aspekty použivani konopi pro lecebne ucely a jejich strucný vývoj. Kniha dale popisuje lekove formy, ktere je v ramci lekařskeho použiti konopi možne připravit a nadto poskytuje prakticke rady, jakým způsobem je připravky s obsahem konopi možne předepsat (vcetně ukazek receptů). Na zavěr jsou v textu uvedeny možnosti použiti konopi a kanabinoidů ve veterinarni medicině.
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Gestational methylazoxymethanol acetate (MAM) treatment produces offspring with adult phenotype relevant to schizophrenia, including positive- and negative-like symptoms, cognitive deficits, dopaminergic dysfunction, structural and... more
Gestational methylazoxymethanol acetate (MAM) treatment produces offspring with adult phenotype relevant to schizophrenia, including positive- and negative-like symptoms, cognitive deficits, dopaminergic dysfunction, structural and functional abnormalities. Here we show that adult rats prenatally treated with MAM at gestational day 17 display significant increase in dopamine D3 receptor (D3) mRNA expression in prefrontal cortex (PFC), hippocampus and nucleus accumbens, accompanied by increased expression of dopamine D2 receptor (D2) mRNA exclusively in the PFC. Furthermore, a significant change in the blood perfusion at the level of the circle of Willis and hippocampus, paralleled by the enlargement of lateral ventricles, was also detected by magnetic resonance imaging (MRI) techniques. Peripubertal treatment with the non-euphoric phytocannabinoid cannabidiol (30 mg/kg) from postnatal day (PND) 19 to PND 39 was able to reverse in MAM exposed rats: i) the up-regulation of the dopamine D3 receptor mRNA (only partially prevented by haloperidol 0.6 mg/kg/day); and ii) the regional blood flow changes in MAM exposed rats. Molecular modelling predicted that cannabidiol could bind preferentially to dopamine D3 receptor, where it may act as a partial agonist according to conformation of ionic-lock, which is higly conserved in GPCRs. In summary, our results demonstrate that the mRNA expression of both dopamine D2 and D3 receptors is altered in the MAM model; however only the transcript levels of D3 are affected by cannabidiol treatment, likely suggesting that this gene might not only contribute to the schizophrenia symptoms but also represent an unexplored target for the antipsychotic activity of cannabidiol.
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ABSTRACT In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long‐lasting behavioral alterations such as... more
ABSTRACT In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long‐lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, respectively. At the molecular level, an increased cannabinoid receptor type‐1 (CB1) mRNA and protein expression, which might be due to reduction in DNA methylation at the gene promoter in the prefrontal cortex (PFC), coincided with deficits in the social interaction test and in the novel object recognition test in MAM rats. Both the schizophrenia‐like phenotype and altered transcriptional regulation of CB1 receptors were reversed by peripubertal treatment (from PND 19 to PND 39) with the non‐psychotropic phytocannabinoid cannabidiol (30mg/kg/day), or, in part, by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5mg/kg/day), but not with haloperidol (0.6mg/kg/day). These results suggest that early treatment with cannabidiol may prevent both the appearance of schizophrenia‐like deficits as well as CB1 alterations in the PFC at adulthood, supporting that peripubertal cannabidiol treatment might be protective against MAM insult. HIGHLIGHTSPrenatal MAM exposure affects CB1 receptor in the prefrontal cortex of adult rats.Peripubertal cannabidiol treatment prevents behavioral and molecular alterations in MAM rats at adulthood.Peripubertal cannabidiol treatment does not negatively affect control animals.
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Methamphetamine is one of the most popular recreational drugs in Central Europe and is often combined with ethanol. Various interactions between these two substances have been described including the influence of administered ethanol on... more
Methamphetamine is one of the most popular recreational drugs in Central Europe and is often combined with ethanol. Various interactions between these two substances have been described including the influence of administered ethanol on biotransformation of methamphetamine. The aim of the present study was to describe the opposite effect - the influence of methamphetamine on biotransformation of ethanol in rats. Methamphetamine was administered for 10 days (10 mg/kg/day) i.p. and ethanol was delivered as an intragastric bolus (2 g/kg) on the10th day of experiment to both methamphetamine administered rats and control animals. The pharmacokinetic experiment on the whole animal was performed and plasma samples were drawn at the 40th, 120th, 210th and 300th minute after ethanol administration. Ethanol plasmatic levels reached significantly lower values in the 40th and 120th interval when compared to controls. Differences were insignificant in the last two intervals. Our results suggest ...
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Modafinil is a psychostimulant drug prescribed for treatment of narcolepsy. However, it is used as a "smart drug" especially by young adults to increase wakefulness, concentration and mental performance. Therefore, it can also... more
Modafinil is a psychostimulant drug prescribed for treatment of narcolepsy. However, it is used as a "smart drug" especially by young adults to increase wakefulness, concentration and mental performance. Therefore, it can also be used by women with childbearing potential and its developmental effects can become a concern. The aim of this study was to assess behavioural and immune effects of prenatal modafinil exposure in mice and to evaluate the reaction to methamphetamine exposure on these animals in adult age. Pregnant female mice were given either saline or modafinil (50 mg/kg orally) from gestation day (GD) 3 to GD 10 and then a challenge dose on GD 17. The male offspring were treated analogously at the age of 10 weeks with methamphetamine (2.5 mg/kg orally). Changes in the spontaneous locomotor/exploratory behaviour and anxiogenic profile in the open field test were assessed in naïve animals, after an acute and 8th modafinil dose and the challenge dose following a 7-d...