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Stanislaw J Czuczwar - One of the best experts on this subject based on the ideXlab platform.
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EFFECT OF SOME CONVULSANTS ON THE PROTECTIVE ACTIVITY OF LORECLEZOLE AND ITS COMBINATIONS WITH VALPROATE OR Clonazepam IN AMYGDALA-KINDLED RATS
2013Co-Authors: Pol J. Pharmacol, Kinga K. Borowicz, Stanislaw J CzuczwarAbstract:Effect of some convulsants on the protective activity of loreclezole and its combinations with valproate or Clonazepam in amygdala-kindled rats. K.K. BOROWICZ, S.J. CZUCZWAR. Pol. J. Pharmacol., 2003, 55, 727–733. Loreclezole (5 mg/kg) exerted a significant protective action in amygdala-kindled rats, reducing both seizure and afterdischarge durations. The combinations of loreclezole (2.5 mg/kg) with valproate, Clonazepam, or carbamazepine (applied at their subprotective doses) also exhibited antiseizure effect in this test. However, only two first combinations occurred to be of pharmacodynamic nature. Among several chemoconvulsants, bicuculline, N-methyl-D-aspartic acid and BAY k-8644 (the opener of L-type calcium channels) reversed the protective activity of loreclezole alone and its combination with valproate. On the other hand, bicuculline, aminophylline and BAY k-8644 inhibited the anticonvulsive action of loreclezole combined with Clonazepam. The results support the hypothesis that the protective activity of loreclezole and its combinations with other antiepileptics may involve potentiation of GABAergic neurotransmission and blockade of L-type of calcium channels
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7 nitroindazole a nitric oxide synthase inhibitor enhances the anticonvulsive action of ethosuximide and Clonazepam against pentylenetetrazol induced convulsions
Journal of Neural Transmission, 2000Co-Authors: Kinga K. Borowicz, Zdzisław Kleinrok, Jarogniew J. Łuszczki, Stanislaw J CzuczwarAbstract:The interaction of 7-nitroindazole (7-NI), a nitric oxide synthase (NOS) inhibitor, with the protective activity of conventional antiepileptics against pentylenetetrazol (PTZ)-induced seizures was tested in mice. Alone, 7-nitroindazole (up to 50 mg/kg) was ineffective in this model of experimental epilepsy. However, it potentiated the anticonvulsive activity of ethosuximide and Clonazepam, significantly reducing their ED50s against PTZ-induced convulsions (from 144 to 76 mg/kg, and from 0.05 to 0.016 mg/kg, respectively). Conversely, the protective actions of valproate and phenobarbital were not affected by the NOS inhibitor. Since the nitric oxide precursor, L-arginine, did not reverse the action of 7-NI on ethosuximide or Clonazepam, an involvement of central NO does not seem probable. Neither ethosuximide nor Clonazepam, administered at their ED50s (144 and 0.05 mg/kg, respectively), produced significant adverse effects as regards motor coordination (chimney test) and long-term memory (passive avoidance task). Also 7-NI (50 mg/kg) and its combinations with ethosuximide and Clonazepam (providing a 50% protection against PTZ-evoked seizures) did not disturb motor and mnemonic performance in mice. The interaction at the pharmacokinetic level does not seem probable, at least in the case of ethosuximide, because the NOS inhibitor did not interfere with its plasma or brain concentrations.
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7 nitroindazole a nitric oxide synthase inhibitor enhances the anticonvulsive action of ethosuximide and Clonazepam against pentylenetetrazol induced convulsions
Journal of Neural Transmission, 2000Co-Authors: Kinga K. Borowicz, Zdzisław Kleinrok, Jarogniew J łuszczki, Stanislaw J CzuczwarAbstract:The interaction of 7-nitroindazole (7-NI), a nitric oxide synthase (NOS) inhibitor, with the protective activity of conventional antiepileptics against pentylenetetrazol (PTZ)-induced seizures was tested in mice. Alone, 7-nitroindazole (up to 50 mg/kg) was ineffective in this model of experimental epilepsy. However, it potentiated the anticonvulsive activity of ethosuximide and Clonazepam, significantly reducing their ED50s against PTZ-induced convulsions (from 144 to 76 mg/kg, and from 0.05 to 0.016 mg/kg, respectively). Conversely, the protective actions of valproate and phenobarbital were not affected by the NOS inhibitor. Since the nitric oxide precursor, L-arginine, did not reverse the action of 7-NI on ethosuximide or Clonazepam, an involvement of central NO does not seem probable. Neither ethosuximide nor Clonazepam, administered at their ED50s (144 and 0.05 mg/kg, respectively), produced significant adverse effects as regards motor coordination (chimney test) and long-term memory (passive avoidance task). Also 7-NI (50 mg/kg) and its combinations with ethosuximide and Clonazepam (providing a 50% protection against PTZ-evoked seizures) did not disturb motor and mnemonic performance in mice. The interaction at the pharmacokinetic level does not seem probable, at least in the case of ethosuximide, because the NOS inhibitor did not interfere with its plasma or brain concentrations.
Farhad Ahmadi - One of the best experts on this subject based on the ideXlab platform.
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silver nanofibers ionic liquid nanocomposite based electrochemical sensor for detection of Clonazepam via electrochemically amplified detection
Microchemical Journal, 2019Co-Authors: Alireza Khoshroo, Laleh Hosseinzadeh, Ali Sobhaninasab, Mehdi Rahiminasrabadi, Farhad AhmadiAbstract:Abstract In this work, an electrochemical sensing platform based on nanostructured silver fibers (SFs) and Ionic liquid (IL) composite (SFs − IL) was developed for electrochemical sensor. Glassy carbon electrode modified with SFs − IL nanocomposite and used to development of the electrochemical sensor for detection of Clonazepam, which increase the reduction peak currents of Clonazepam and lowering in the peak potential of Clonazepam. The improvement of electrochemical response to Clonazepam reduction was found at SFs − IL modified electrode, revealing the synergetic effect of SFs and IL. The properties of catalyst materials were characterized by scanning electron microscope, X-ray diffraction, electrochemical impedance spectroscopy, cyclic voltammetry, differential pulse voltammetry, chronoamperometry and electrochemical impedance spectroscopy. SFs − IL modified electrode offers a wide linear range from 0.1 to 250 μM with a low detection limit of 66 nM, and acceptable reproducibility and stability. Furthermore, the real sample analysis revealed satisfactory recovery for the detection of Clonazepam in pharmaceutical formulation, serum and urine samples.
Kinga K. Borowicz - One of the best experts on this subject based on the ideXlab platform.
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EFFECT OF SOME CONVULSANTS ON THE PROTECTIVE ACTIVITY OF LORECLEZOLE AND ITS COMBINATIONS WITH VALPROATE OR Clonazepam IN AMYGDALA-KINDLED RATS
2013Co-Authors: Pol J. Pharmacol, Kinga K. Borowicz, Stanislaw J CzuczwarAbstract:Effect of some convulsants on the protective activity of loreclezole and its combinations with valproate or Clonazepam in amygdala-kindled rats. K.K. BOROWICZ, S.J. CZUCZWAR. Pol. J. Pharmacol., 2003, 55, 727–733. Loreclezole (5 mg/kg) exerted a significant protective action in amygdala-kindled rats, reducing both seizure and afterdischarge durations. The combinations of loreclezole (2.5 mg/kg) with valproate, Clonazepam, or carbamazepine (applied at their subprotective doses) also exhibited antiseizure effect in this test. However, only two first combinations occurred to be of pharmacodynamic nature. Among several chemoconvulsants, bicuculline, N-methyl-D-aspartic acid and BAY k-8644 (the opener of L-type calcium channels) reversed the protective activity of loreclezole alone and its combination with valproate. On the other hand, bicuculline, aminophylline and BAY k-8644 inhibited the anticonvulsive action of loreclezole combined with Clonazepam. The results support the hypothesis that the protective activity of loreclezole and its combinations with other antiepileptics may involve potentiation of GABAergic neurotransmission and blockade of L-type of calcium channels
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7 nitroindazole a nitric oxide synthase inhibitor enhances the anticonvulsive action of ethosuximide and Clonazepam against pentylenetetrazol induced convulsions
Journal of Neural Transmission, 2000Co-Authors: Kinga K. Borowicz, Zdzisław Kleinrok, Jarogniew J. Łuszczki, Stanislaw J CzuczwarAbstract:The interaction of 7-nitroindazole (7-NI), a nitric oxide synthase (NOS) inhibitor, with the protective activity of conventional antiepileptics against pentylenetetrazol (PTZ)-induced seizures was tested in mice. Alone, 7-nitroindazole (up to 50 mg/kg) was ineffective in this model of experimental epilepsy. However, it potentiated the anticonvulsive activity of ethosuximide and Clonazepam, significantly reducing their ED50s against PTZ-induced convulsions (from 144 to 76 mg/kg, and from 0.05 to 0.016 mg/kg, respectively). Conversely, the protective actions of valproate and phenobarbital were not affected by the NOS inhibitor. Since the nitric oxide precursor, L-arginine, did not reverse the action of 7-NI on ethosuximide or Clonazepam, an involvement of central NO does not seem probable. Neither ethosuximide nor Clonazepam, administered at their ED50s (144 and 0.05 mg/kg, respectively), produced significant adverse effects as regards motor coordination (chimney test) and long-term memory (passive avoidance task). Also 7-NI (50 mg/kg) and its combinations with ethosuximide and Clonazepam (providing a 50% protection against PTZ-evoked seizures) did not disturb motor and mnemonic performance in mice. The interaction at the pharmacokinetic level does not seem probable, at least in the case of ethosuximide, because the NOS inhibitor did not interfere with its plasma or brain concentrations.
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7 nitroindazole a nitric oxide synthase inhibitor enhances the anticonvulsive action of ethosuximide and Clonazepam against pentylenetetrazol induced convulsions
Journal of Neural Transmission, 2000Co-Authors: Kinga K. Borowicz, Zdzisław Kleinrok, Jarogniew J łuszczki, Stanislaw J CzuczwarAbstract:The interaction of 7-nitroindazole (7-NI), a nitric oxide synthase (NOS) inhibitor, with the protective activity of conventional antiepileptics against pentylenetetrazol (PTZ)-induced seizures was tested in mice. Alone, 7-nitroindazole (up to 50 mg/kg) was ineffective in this model of experimental epilepsy. However, it potentiated the anticonvulsive activity of ethosuximide and Clonazepam, significantly reducing their ED50s against PTZ-induced convulsions (from 144 to 76 mg/kg, and from 0.05 to 0.016 mg/kg, respectively). Conversely, the protective actions of valproate and phenobarbital were not affected by the NOS inhibitor. Since the nitric oxide precursor, L-arginine, did not reverse the action of 7-NI on ethosuximide or Clonazepam, an involvement of central NO does not seem probable. Neither ethosuximide nor Clonazepam, administered at their ED50s (144 and 0.05 mg/kg, respectively), produced significant adverse effects as regards motor coordination (chimney test) and long-term memory (passive avoidance task). Also 7-NI (50 mg/kg) and its combinations with ethosuximide and Clonazepam (providing a 50% protection against PTZ-evoked seizures) did not disturb motor and mnemonic performance in mice. The interaction at the pharmacokinetic level does not seem probable, at least in the case of ethosuximide, because the NOS inhibitor did not interfere with its plasma or brain concentrations.
Joëlle Micallef - One of the best experts on this subject based on the ideXlab platform.
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evidence of Clonazepam abuse liability results of the tools developed by the french centers for evaluation and information on pharmacodependence ceip network
Fundamental & Clinical Pharmacology, 2011Co-Authors: Elisabeth Frauger, Vanessa Pauly, Vincent Pradel, Frank Rouby, Xavier Thirion, Jocelyne Arditti, Maryse Lapeyre Mestre, Joëlle MicallefAbstract:Recent observations suggest the existence of Clonazepam abuse. To determine its importance in France, a quantitative and systematic synthesis of all Clonazepam data of several epidemiological tools of the Centers for Evaluation and Information on Pharmacodependence (CEIP) network has been performed in comparison with data on others benzodiazepines (BZD). Data on Clonazepam and other BZD have been analysed from different epidemiological tools: OSIAP survey that identifies drugs obtained by means of falsified prescriptions, Observation of Illegal Drugs and Misuse of Psychotropic Medications (OPPIDUM) survey that describes modalities of use and data from regional French health reimbursement system. In OSIAP survey, the proportion of Clonazepam falsified prescriptions among all BZD falsified prescriptions increased. During the 2006 OPPIDUM survey, the analysis of the BZD modalities of use highlights Clonazepam abuse liability (for example 23% of illegal acquisition), in second rank after flunitrazepam. Studies based on data from the French health reimbursed system show that 1.5% of subjects with Clonazepam dispensing had a deviant behaviour. Among BZD, Clonazepam has the second most important doctor-shopping indicator (3%) after flunitrazepam. All these data provide some arguments in favour of Clonazepam abuse liability in real life and the necessity to reinforce its monitoring.
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Estimation of Clonazepam abuse liability: a new method using a reimbursed drug database.
International Clinical Psychopharmacology, 2009Co-Authors: Elisabeth Frauger, Vanessa Pauly, François Natali, Vincent Pradel, Patrick Reggio, Frank Rouby, Hervé Coudert, Xavier Thirion, Joëlle MicallefAbstract:: Some observations suggest the existence of Clonazepam abuse. The aim of this study was to assess its magnitude in real life by a new method, using a prescription database, and to assess its evolution between 2001 and 2006. Individuals from a region affiliated to the French health reimbursement system, who had a prescription of Clonazepam reimbursed between 1 January and 15 February of two selected years were included. Their deliveries were monitored over a 9-month period. After a descriptive analysis, a clustering method illustrated by a factorial analysis was used to identify different subgroups of Clonazepam consumers. An increase of 82% in participants who had a delivery of Clonazepam between 2001 and 2006 was observed. Using the clustering method, this study identified some deviant participants. This group comprises a higher proportion of males, benzodiazepine users, and buprenorphine users. The number of deliveries by different prescribers and pharmacies are higher. The proportion of deviant participants increased between 2001 and 2006 (from 0.86 to 1.38%). Our method can be used to assess the magnitude of abuse liability of Clonazepam and is also interesting for following its evolution, two important keys for assessing patterns of abuse.
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detournement d usage du Clonazepam rivotril tendances recentes
Therapie, 2006Co-Authors: Elisabeth Frauger, François Natali, Vincent Pradel, Patrick Reggio, Xavier Thirion, Joëlle MicallefAbstract:Recent observations suggest the existence of Clonazepam abuse. In order to determine the importance of this practice and the characteristics of these consumers, a study has been carried out, based on data from the Provence-Alpes-Cote-d'Azur and Corsica health reimbursement system. Individuals from these regions affiliated to the French health reimbursement system, who have had a prescription of Clonazepam reimbursed between January 1, 2001 and February 15, 2001, have been selected. The deliveries have been monitored over a 9 month-period. 9381 subjects have been selected. A sub-group of 1.5 per cent subjects with a deviant behaviour has been identified by factorial analysis and has been compared to the sub-group without deviant behaviour. The subjects with deviant behaviour are younger and mostly male. The dosage of Clonazepam is higher (10.8 mg per day versus 2.1 mg per day) with a significantly higher proportion of benzodiazepine and high-dose buprenorphine. The number of deliveries is higher (19.4 versus 5.9) as well as the number of different physicians (4.5 versus 1.5) and pharmacies (5.9 versus 1.3). This study provides some arguments in favor of the potential of abuse and dependence of Clonazepam and the necessity to reinforce its monitoring. This information requires to be relayed to health professionals.
Murray B Stein - One of the best experts on this subject based on the ideXlab platform.
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a double blind randomized controlled trial of augmentation and switch strategies for refractory social anxiety disorder
American Journal of Psychiatry, 2014Co-Authors: Mark H Pollack, Michael Van Ameringen, Naomi M Simon, John Worthington, Elizabeth A Hoge, Aparna Keshaviah, Murray B SteinAbstract:Adding Clonazepam increases the likelihood of response in patients with social anxiety disorder who remain symptomatic after a trial with an SSRI, supporting the common clinical practice of combining a benzodiazepine with an SSRI. Among 181 nonresponders to sertraline alone, those who had up to 3 mg/day of Clonazepam added to sertraline had a response rate of 56% after 12 weeks, compared with 36% for those who continued to take sertraline alone and 46% for patients switched to venlafaxine. Remission rates were 27%, 17%, and 19%, respectively, but did not show a statistical difference.
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double blind placebo controlled assessment of combined Clonazepam with paroxetine compared with paroxetine monotherapy for generalized social anxiety disorder
The Journal of Clinical Psychiatry, 2004Co-Authors: Soraya Seedat, Murray B SteinAbstract:BACKGROUND Generalized social anxiety disorder (GSAD) is a pervasive form of social anxiety that affects approximately 5% of persons in the community. Among evidence-based pharmacologic treatments for the disorder, selective serotonin reuptake inhibitors (SSRIs) have become widely used and are known to be efficacious. Monotherapy with the benzodiazepine Clonazepam is also efficacious for GSAD, but the adjunctive use of Clonazepam with an SSRI to potentially improve outcomes has not been studied to date. METHOD Twenty-eight patients (22 men and 6 women) with DSM-IV-defined GSAD were randomly assigned to receive double-blind Clonazepam (or placebo), 1.0 to 2.0 mg/day (divided b.i.d.) along with open-label paroxetine, 20 to 40 mg/day, for 10 weeks. A 2-week taper of double-blind medication was followed by an additional 8 weeks of open-label paroxetine treatment (during which the dose of paroxetine could be increased to a maximum of 50 mg/day). Twenty-three patients (82%) met DSM-IV criteria for avoidant personality disorder. The patients' mean +/- SD age was 31.2 +/- 7.7 years, and their mean duration of illness was 12.1 +/- 5.8 years. Data were gathered from August 2001 to April 2002. RESULTS Nineteen (68%) of 28 patients completed treatment. At the end of the 10-week double-blind treatment, there was a trend (p <.06) favoring the paroxetine/Clonazepam group, who had a 79% response rate (Clinical Global Impressions-Global Improvement scale [CGI-I] score of 1 or 2) compared with a 43% response rate for the paroxetine/placebo group. However, no significant differences on other outcome measures were noted between the 2 groups in an intent-to-treat analysis, in terms of either very early (2-4 weeks) or not as early (5-10 weeks) responses during treatment. Dropout rates due to adverse events were rare (1 patient in each group), indicating that the paroxetine/Clonazepam combination was well tolerated. CONCLUSION Coadministration of Clonazepam with an SSRI, in contrast to findings in panic disorder, did not lead to more rapid resolution of symptoms in GSAD. On the other hand, there is some evidence that the Clonazepam-added group had superior global outcomes (e.g., as measured on the CGI-I), although power to detect such differences in this study was small. These observations suggest that a role for adjunctive benzodiazepines in patients with GSAD (e.g., for augmenting SSRI partial response or nonresponse) is deserving of further controlled investigation.