The Experts below are selected from a list of 6693 Experts worldwide ranked by ideXlab platform
Jarogniew J. Luszczki - One of the best experts on this subject based on the ideXlab platform.
-
effects of win 55 212 2 a synthetic cannabinoid cb1 and CB2 Receptor Agonist on the anticonvulsant activity of various novel antiepileptic drugs against 6 hz induced psychomotor seizures in mice
Pharmacology Biochemistry and Behavior, 2015Co-Authors: Magdalena Florekluszczki, Aleksandra Wlaz, Miroslaw Zagaja, Marta Andresmach, Maria W Kondratwrobel, Jarogniew J. LuszczkiAbstract:The purpose of this study was to determine the influence of WIN 55,212-2 mesylate (WIN—a non-selective cannabinoid CB1 and CB2 Receptor Agonist) on the anticonvulsant activity of various second- and third-generation antiepileptic drugs (i.e., gabapentin, lacosamide, levetiracetam, oxcarbazepine, pregabalin and tiagabine) in the mouse 6 Hz-induced psychomotor seizure model. Psychomotor seizures were evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Additionally, total brain antiepileptic drug concentrations were measured. Results indicate that WIN (5 mg/kg, administered i.p.) significantly potentiated the anticonvulsant action of gabapentin (P < 0.05) and levetiracetam (P < 0.01), but not that of lacosamide, oxcarbazepine, pregabalin or tiagabine in the mouse psychomotor seizure model. Moreover, WIN (2.5 mg/kg) had no significant effect on the anticonvulsant activity of all tested antiepileptic drugs in the 6 Hz test in mice. Measurement of total brain antiepileptic drug concentrations revealed that WIN (5 mg/kg) had no impact on gabapentin or levetiracetam total brain concentrations, indicating the pharmacodynamic nature of interaction between these antiepileptic drugs in the mouse 6 Hz model. In conclusion, WIN in combination with gabapentin and levetiracetam exerts beneficial anticonvulsant pharmacodynamic interactions in the mouse psychomotor seizure model.
-
Effects of WIN 55,212-2 (a non-selective cannabinoid CB1 and CB2 Receptor Agonist) on the protective action of various classical antiepileptic drugs in the mouse 6 Hz psychomotor seizure model
Journal of Neural Transmission, 2014Co-Authors: Magdalena Florek-luszczki, Aleksandra Wlaz, Maria W. Kondrat-wróbel, Piotr Tutka, Jarogniew J. LuszczkiAbstract:The aim of this study was to characterize the influence of WIN 55,212-2 (WIN—a non-selective cannabinoid CB1 and CB2 Receptor Agonist) on the anticonvulsant effects of various classical antiepileptic drugs (clobazam, clonazepam, phenobarbital and valproate) in the mouse 6 Hz-induced psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Drug-related adverse effects were ascertained by use of the chimney test (evaluating motor performance), step-through passive avoidance task (assessing learning) and grip-strength test (evaluating skeletal muscular strength). Total brain concentrations of antiepileptic drugs were measured by fluorescence polarization immunoassay to ascertain any pharmacokinetic contribution to the observed antiseizure effect. Results indicate that WIN (5 mg/kg, administered intraperitoneally) significantly enhanced the anticonvulsant action of clonazepam (P
-
effects of win 55 212 2 a non selective cannabinoid cb1 and CB2 Receptor Agonist on the protective action of various classical antiepileptic drugs in the mouse 6 hz psychomotor seizure model
Journal of Neural Transmission, 2014Co-Authors: Magdalena Florekluszczki, Aleksandra Wlaz, Piotr Tutka, Maria W Kondratwrobel, Jarogniew J. LuszczkiAbstract:The aim of this study was to characterize the influence of WIN 55,212-2 (WIN—a non-selective cannabinoid CB1 and CB2 Receptor Agonist) on the anticonvulsant effects of various classical antiepileptic drugs (clobazam, clonazepam, phenobarbital and valproate) in the mouse 6 Hz-induced psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Drug-related adverse effects were ascertained by use of the chimney test (evaluating motor performance), step-through passive avoidance task (assessing learning) and grip-strength test (evaluating skeletal muscular strength). Total brain concentrations of antiepileptic drugs were measured by fluorescence polarization immunoassay to ascertain any pharmacokinetic contribution to the observed antiseizure effect. Results indicate that WIN (5 mg/kg, administered intraperitoneally) significantly enhanced the anticonvulsant action of clonazepam (P < 0.001), phenobarbital (P < 0.05) and valproate (P < 0.05), but not that of clobazam in the mouse 6 Hz model. Moreover, WIN (2.5 mg/kg) significantly potentiated the anticonvulsant action of clonazepam (P < 0.01), but not that of clobazam, phenobarbital or valproate in the 6 Hz test in mice. None of the investigated combinations of WIN with antiepileptic drugs was associated with any concurrent adverse effects with regard to motor performance, learning or muscular strength. Pharmacokinetic experiments revealed that WIN had no impact on total brain concentrations of antiepileptic drugs in mice. These preclinical data would suggest that WIN in combination with clonazepam, phenobarbital and valproate is associated with beneficial anticonvulsant pharmacodynamic interactions in the mouse 6 Hz-induced psychomotor seizure test.
Gerald W. Zamponi - One of the best experts on this subject based on the ideXlab platform.
-
analgesic effect of a mixed t type channel inhibitor CB2 Receptor Agonist
Molecular Pain, 2013Co-Authors: Vinicius M. Gadotti, Haitao You, Ravil R. Petrov, Philippe Diaz, Daniel N Berger, Gerald W. ZamponiAbstract:Background Cannabinoid Receptors and T-type calcium channels are potential targets for treating pain. Here we report on the design, synthesis and analgesic properties of a new mixed cannabinoid/T-type channel ligand, NMP-181.
-
Analgesic effect of a mixed T-type channel inhibitor/CB2 Receptor Agonist
Molecular Pain, 2013Co-Authors: Vinicius M. Gadotti, Haitao You, Ravil R. Petrov, N. Daniel Berger, Philippe Diaz, Gerald W. ZamponiAbstract:Background Cannabinoid Receptors and T-type calcium channels are potential targets for treating pain. Here we report on the design, synthesis and analgesic properties of a new mixed cannabinoid/T-type channel ligand, NMP-181.
Mohammad-reza Zarrindast - One of the best experts on this subject based on the ideXlab platform.
-
Blockade of dorsal hippocampal dopamine Receptors inhibits state-dependent learning induced by cannabinoid Receptor Agonist in mice.
Neuroscience Research, 2010Co-Authors: Mohammad-reza Zarrindast, Mania Dorrani, Razieh Lachinani, Ameneh RezayofAbstract:Abstract To clarify the interaction between cannabinnoid CB1 Receptors and the dopaminergic system in memory processes, the effects of dopamine Receptor agents on the state-dependent learning induced by the non-selective CB1/CB2 Receptor Agonist, WIN55,212-2 have been investigated in mice. Animals implanted with unilateral cannula at the CA1 region of the dorsal hippocampus and microinjected with WIN55,212-2 and/or dopaminergic agents, were tested using a single-trial step-down passive avoidance task. Intra-CA1 microinjections of WIN55,212-2 (0.1–1 μg/mouse) immediately after training, decreased the step-down latency, indicating an amnesic effect of the drug. The amnesia was reversed by pre-test administration of the drug, suggesting state-dependent learning by the cannabinoid. Pre-test microinjection of apomorphine, a D1/D2 dopamine Receptor Agonist (0.1–0.3 μg/mouse) into the CA1 region reversed the amnesia induced by post-training WIN55,212-2 (1 μg/mouse). Moreover, pre-test co-administration of apomorphine with an ineffective dose of WIN55,212-2 (0.01 μg/mouse), showed a reversion of the impairment on retention performance. Pre-test administration of the same doses of apomorphine did not show any response by itself. Pre-test intra-CA1 administration of a D1 dopamine Receptor antAgonist, SCH23390 (0.05–0.3 μg/mouse) or D2 dopamine Receptor antAgonist, sulpiride (0.125–0.5 μg/mouse) inhibited the expression of WIN55,212-2-induced state-dependent learning. Pre-test microinjection of the same doses of SCH23390 or sulpiride had no effect on WIN55,212-2-induced amnesia. Moreover, single injection of SCH23390 (0.2 and 0.3 μg/mouse) or sulpiride (0.125 μg/mouse) decreased memory retrieval. The results suggest that the dorsal hippocampal dopaminergic system participates in the modulation of WIN55,212-2-induced state-dependent learning.
-
anxiety like behavior induced by histaminergic agents can be prevented by cannabinoidergic win55 212 2 injected into the dorsal hippocampus in mice
Pharmacology Biochemistry and Behavior, 2010Co-Authors: Mohammad-reza Zarrindast, Morteza Piri, Mohammad Nasehi, Payvand BinaAbstract:Abstract In the present study, we investigate the effects of the histaminergic system and cannabinoid Receptor agents on anxiety-related behaviors and their interactions using the hole-board test on mice. Bilateral intra-CA1 administration of the CB1/CB2 Receptor Agonist, WIN55, 212-2 (0.1–0.5 µg/mouse) did not modify exploratory behaviors in mice. On the other hand, intra-CA1 administration of CB1 Receptor antAgonist, AM251 (25 and 50 ng/mouse) or histamine, pyrilamine and ranitidine (5–10 µg/mouse) decreased the amount of head-dipping and increased the first head-dip, suggesting an anxiogenic-like response. Furthermore, our present data indicated that the co-administration of WIN55, 212-2 (0.25 µg/mouse) with histaminergic agents, decreased the anxiogenic-like response of an effective dose (5 µg/mouse) of histamine and pyrilamine, but not that of ranitidine. In addition, the results demonstrated that co-administration of an ineffective dose of AM251 (15 ng/mouse) with histaminergic drugs did not alter the response induced by an ineffective dose (3.75 µg/mouse) of either histamine or pyrilamine and ranitidine. In all experiments and doses, locomotor activity and other exploratory behaviors were not significantly changed. In conclusion, our results showed that there is a chance of partial interaction between the cannabinoidergic and the histaminergic systems of the dorsal hippocampus on anxiogenic/anxiolytic-like behaviors in hole-board test.
-
influence of nicotinic Receptor modulators on CB2 cannabinoid Receptor Agonist jwh133 induced antinociception in mice
Behavioural Pharmacology, 2007Co-Authors: Mohammad Reza Jafari, Mohammad-reza Zarrindast, Somaye Golmohammadi, Fereshteh Ghiasvand, Bijan DjahanguiriAbstract:Delta9-tetrahydrocannabinol is the active component in cannabis and has long been associated with pain relief. This effect is believed to be mediated through central and peripheral CB1 and peripheral CB2 Receptors. We have explored the possible antinociceptive effect of a CB2 Receptor Agonist, JWH133, using the formalin test in mice. The drug was administered by the intracerebroventricular and intraperitoneal routes. Although no antinociceptive effect was observed after intracerebroventricular administration of JWH133, when the drug was administered by the intraperitoneal route, it produced an analgesic effect. The influence of nicotinic cholinergic Receptor modulators, nicotine and mecamylamine, on antinociceptive effect of JWH133 was also studied. Nicotine increased and mecamylamine decreased the antinociceptive effect of JWH133. It is concluded that JWH133-induced analgesia is influenced by nicotinic cholinergic Receptor activity. Behavioural Pharmacology 18:691-697 (C) 2007 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
-
influence of intracerebroventricular administration of cannabinergic drugs on morphine state dependent memory in the step down passive avoidance test
Behavioural Pharmacology, 2006Co-Authors: Mohammad-reza Zarrindast, Katayoun Kangarluhaghighi, Azita Khalilzadeh, Soheila FazlitabaeiAbstract:The effects of cannabinergic drugs on morphine state-dependent memory of passive avoidance task were examined in mice. Pre-training (0.25, 0.5 and 5 mg/kg) and post-training (5 mg/kg) administration of morphine impaired memory retrieval on the test day. Impairment of memory retrieval by morphine (5 mg/kg) on the test day was reversed by pre-test administration of the same dose of the opioid. The pre-test intracerebroventricular administration of the cannabinoid CB1/CB2 Receptor Agonist (WIN55,212-2) (0.75 and 1 microg/mouse) not only mimicked the effect of pre-test morphine treatment, but also increased this action of the opioid. Furthermore, the pre-test intracerebroventricular administration of CB1 Receptor antAgonist (AM251) (20 and 100 ng/mouse) prevented the restoration of memory by morphine. Pre-training administration of WIN55,212-2 (1 microg/mouse) led to state-dependent learning with impaired memory retrieval on the test day as well, which was reversed by pre-test administration of the drug (0.5, 0.75 and 1 microg/mouse) or morphine (1 and 5 mg/kg). Restoration of impairment induced by WIN55,212-2 was decreased by both the opioid Receptor antAgonists, naloxone (0.01 microg/mouse) and AM251 (20 and 100 ng/mouse). In conclusion, the improvement of memory retrieval by morphine treatment on the test day seems to be induced, at least in part, by the cannabinoid CB1 Receptors.
Vinicius M. Gadotti - One of the best experts on this subject based on the ideXlab platform.
-
analgesic effect of a mixed t type channel inhibitor CB2 Receptor Agonist
Molecular Pain, 2013Co-Authors: Vinicius M. Gadotti, Haitao You, Ravil R. Petrov, Philippe Diaz, Daniel N Berger, Gerald W. ZamponiAbstract:Background Cannabinoid Receptors and T-type calcium channels are potential targets for treating pain. Here we report on the design, synthesis and analgesic properties of a new mixed cannabinoid/T-type channel ligand, NMP-181.
-
Analgesic effect of a mixed T-type channel inhibitor/CB2 Receptor Agonist
Molecular Pain, 2013Co-Authors: Vinicius M. Gadotti, Haitao You, Ravil R. Petrov, N. Daniel Berger, Philippe Diaz, Gerald W. ZamponiAbstract:Background Cannabinoid Receptors and T-type calcium channels are potential targets for treating pain. Here we report on the design, synthesis and analgesic properties of a new mixed cannabinoid/T-type channel ligand, NMP-181.
Carmen Guaza - One of the best experts on this subject based on the ideXlab platform.
-
a cb1 CB2 Receptor Agonist win 55 212 2 exerts its therapeutic effect in a viral autoimmune model of multiple sclerosis by restoring self tolerance to myelin
Neuropharmacology, 2012Co-Authors: Angel Arevalomartin, Eduardo Molinaholgado, Carmen GuazaAbstract:Abstract Infection of mice with Theiler's murine encephalomyelitis virus (TMEV) leads to the development of TMEV-induced demyelinating disease (TMEV-IDD), an autoimmune, demyelinating and neurodegenerative pathology that serves as a model of multiple sclerosis. Activation of endogenous CB1/CB2 cannabinoid Receptors inhibits inflammation and improves the clinical status of TMEV-IDD animals. In the present study, mice with established TMEV-IDD were treated with the CB1/CB2 Receptor Agonist WIN 55,212-2 (WIN), which restored self-tolerance to a myelin self-antigen while ameliorating the disease in a long-term manner. Accordingly, disruption of self-tolerance with cyclophosphamide provoked chronic relapse. Furthermore, transfer of splenocytes from WIN-treated TMEV-IDD mice to TMEV-infected mice at disease onset prevented the autoimmune inflammatory response and motor impairment. The therapeutic effect of WIN correlated with a decrease in the activation of CD4+CD25+Foxp3− T cells and an increase in regulatory CD4+CD25+Foxp3+ T cells in the CNS, along with alterations in the cytokine and chemokine milieu. These findings demonstrate for the first time that the suppression of autoimmune responses to myelin antigens underlies the therapeutic effect of CB1/CB2 cannabinoid Agonists in the treatment of multiple sclerosis.
-
A CB1/CB2 Receptor Agonist, WIN 55,212-2, exerts its therapeutic effect in a viral autoimmune model of multiple sclerosis by restoring self-tolerance to myelin
Neuropharmacology, 2012Co-Authors: Angel Arevalo-martin, Eduardo Molina-holgado, Carmen GuazaAbstract:Abstract Infection of mice with Theiler's murine encephalomyelitis virus (TMEV) leads to the development of TMEV-induced demyelinating disease (TMEV-IDD), an autoimmune, demyelinating and neurodegenerative pathology that serves as a model of multiple sclerosis. Activation of endogenous CB1/CB2 cannabinoid Receptors inhibits inflammation and improves the clinical status of TMEV-IDD animals. In the present study, mice with established TMEV-IDD were treated with the CB1/CB2 Receptor Agonist WIN 55,212-2 (WIN), which restored self-tolerance to a myelin self-antigen while ameliorating the disease in a long-term manner. Accordingly, disruption of self-tolerance with cyclophosphamide provoked chronic relapse. Furthermore, transfer of splenocytes from WIN-treated TMEV-IDD mice to TMEV-infected mice at disease onset prevented the autoimmune inflammatory response and motor impairment. The therapeutic effect of WIN correlated with a decrease in the activation of CD4+CD25+Foxp3− T cells and an increase in regulatory CD4+CD25+Foxp3+ T cells in the CNS, along with alterations in the cytokine and chemokine milieu. These findings demonstrate for the first time that the suppression of autoimmune responses to myelin antigens underlies the therapeutic effect of CB1/CB2 cannabinoid Agonists in the treatment of multiple sclerosis.