The Experts below are selected from a list of 141 Experts worldwide ranked by ideXlab platform
Mike Briley - One of the best experts on this subject based on the ideXlab platform.
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indirect dopaminergic effects of Tofisopam a 2 3 benzodiazepine and their inhibition by lithium
Journal of Pharmacy and Pharmacology, 2011Co-Authors: Philippe Chopin, Antoine Stenger, Jeanpierre Couzinier, Mike BrileyAbstract:Tofisopam, a 2,3-benzodiazepine, has been shown to have anxiolytic activity. However, in contrast to the widely used 1,4-benzodiazepines, it has no anticonvulsant, sedative or muscle relaxant effects. Tofisopam enhanced the behavioural actions of various dopaminergic drugs, both direct agonists, such as apomorphine (climbing behaviour in mice), and indirect agonists, such as (+)-amphetamine and amineptine (jumping behaviour in mice). Chronic treatment with lithium abolished the Tofisopam-induced increase in the activity of these dopaminergic drugs. Thus Tofisopam appears to induce acutely an increase in the sensitivity of central dopaminergic receptors which can be prevented by pretreatment with lithium.
Manabu Yoshimura - One of the best experts on this subject based on the ideXlab platform.
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effect of Tofisopam on heart rate variability
Current Therapeutic Research-clinical and Experimental, 1993Co-Authors: Tadashi Nakanishi, Masato Nishimura, Hakuo Takahashi, Manabu YoshimuraAbstract:Abstract We evaluated the effects of Tofisopam, a drug that modulates autonomic nerve function, on heart rate variability in 27 patients (12 men and 15 women; mean age, 71 ± 12 years) with a standard deviation of the R-R interval measured at 5-minute intervals (SDANN) of ⩽80 msec on 24-hour electrocardiograms (ECGs). After a control 24-hour ECG was recorded, patients were treated with Tofisopam at a dosage of 150 mg/day. After 2 weeks of treatment, 24-hour ECGs were recorded again. The total cardiac rate and the number of ventricular extrasystoles on 24-hour ECGs did not differ between the control and treatment periods. The SDANN was ⩽80 msec (mean, 62.4 ± 14.7 msec) in all patients during the control period but increased significantly after Tofisopam administration (84.8 ± 27.4 msec; P
Masahiro Murakami - One of the best experts on this subject based on the ideXlab platform.
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synthesis of Tofisopam by way of photoinduced co2 fixation
Chemistry-an Asian Journal, 2019Co-Authors: Yusuke Masuda, Katsuhiko Makita, Naoki Ishida, Masahiro MurakamiAbstract:Herein reported is a unique synthetic route of Tofisopam, an anxiolytic drug containing a 2,3-benzodiazepine core structure. 3,4-Dimethoxypropylbenzene and 3,4-dimethoxybenzoic acid, which are both of plant origin, and CO2 constitute its carbon skeleton. These three renewable substances are united by two C-C bond forming reactions, i.e., a Friedel-Crafts acylation reaction and a photoinduced carboxylation reaction to construct the major carbon framework. Finally, a methyl group is introduced by a Kumada-type cross-coupling reaction to furnish Tofisopam. Various analogs of Tofisopam are readily synthesized by introducing other substituents than a methyl group at the last C-C bond forming step.
Imre Klebovich - One of the best experts on this subject based on the ideXlab platform.
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gas chromatography nitrogen phosphorous detection gc npd assay of Tofisopam in human plasma for pharmacokinetic evaluation
Journal of Pharmaceutical and Biomedical Analysis, 2006Co-Authors: Maria Toth, Sandor Drabant, Judit Tomlo, Andrea Bereczki, Katalin Balogh Nemes, Balint Varga, G Grezal, Geza Lakner, Imre KlebovichAbstract:Abstract Tofisopam (1-(3,4-dimethoxyphenyl)-4-methyl-5-ethyl-7,8-dimethoxy-5H-2,3-benzodiazepine) has been shown to be an effective anxiolytic agent in the wide-ranging clinical practice. A high sensitive gas chromatography nitrogen phosphorous detection (GC-NPD) bioanalytical method was developed and validated for the purpose of pharmacokinetic study of Tofisopam. A liquid–liquid extraction method was used for the sample preparation. The mean recovery for Tofisopam was 69.8% and the inter- and intra-day precision values were well below the 15% limit established for bioanalytical methods. A similar compound, girizopam was used as internal standard. The assay was linear in the 5–500 ng/ml range corresponding to therapeutically relevant plasma levels. The concentrations of the compound were measured in the plasma samples of 12 healthy male volunteers and the pharmacokinetic parameters were determined from the plasma concentration–time data. A rapid absorption and distribution, relatively short biological half-life and considerable inter-individual variation in the plasma concentration levels of parent compound were the main characteristics of the pharmacokinetics of Tofisopam. According to these results, the new (GC-NPD) bioanalytical method proved to be capable of measuring concentration of Tofisopam in human plasma and was successfully applied in a single dose pharmacokinetic study.
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effect of Tofisopam on cyp3a4 enzyme activity on human recombinant 3a4 supersome
Acta pharmaceutica Hungarica, 2005Co-Authors: Maria Toth, Judit Bajnogel, Andras Egyed, Sandor Drabant, Judit Tomlo, Imre KlebovichAbstract:Tofisopam is an anxiolytic agent of the BZD group, chemically 1(3-4 dimethoxyphenyl)-4methyl-5-ethyl-7,8 dimethoxy-5H-2,3-benzodiazepine. TZP differs from the traditional 1,4-benzodiazepines regarding the positions of the nitrogen atoms. Three clinical cases were reported where Tofisopam increased the blood level of immunosuppressive agent leading clinically relevant adverse drug reaction and necessitating reduction of the dose of the drugs or discontinuation of the administration of Tofisopam. The administered immunosuppressive agent is a substrate of the CYP3A4 system, so the effect of Tofisopam on the CYP3A4 enzyme was investigated in vitro using human recombinant CYP3A4 supersome. Benzyoxy-4-(trifluoromethyl)-coumarin (BFC) was used as substrate. Tofisopam in 0.1, 0.25, 0.5, 0.75, 1 and 5 micromol/l concentrations inhibited dose dependently the enzyme activity. Activity inhibition rates were 4%, 29%, 40%, 56%, 61% and 94%, respectively and the IC50 was 0.8 micromol/l. The IC50 of positive control substance ketoconazole was 0.03 micromol/l. In in vitro experiments the inhibitory effect of Tofisopam was lower than that of ketoconazole (potent CYP3A4 inhibitor) with an order of magnitude. According to the in vitro results it could be concluded that Tofisopam is an inhibitor of CYP3A4 but to clarify the clinical importance of this inhibition further human clinical data are needed.
Philippe Chopin - One of the best experts on this subject based on the ideXlab platform.
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indirect dopaminergic effects of Tofisopam a 2 3 benzodiazepine and their inhibition by lithium
Journal of Pharmacy and Pharmacology, 2011Co-Authors: Philippe Chopin, Antoine Stenger, Jeanpierre Couzinier, Mike BrileyAbstract:Tofisopam, a 2,3-benzodiazepine, has been shown to have anxiolytic activity. However, in contrast to the widely used 1,4-benzodiazepines, it has no anticonvulsant, sedative or muscle relaxant effects. Tofisopam enhanced the behavioural actions of various dopaminergic drugs, both direct agonists, such as apomorphine (climbing behaviour in mice), and indirect agonists, such as (+)-amphetamine and amineptine (jumping behaviour in mice). Chronic treatment with lithium abolished the Tofisopam-induced increase in the activity of these dopaminergic drugs. Thus Tofisopam appears to induce acutely an increase in the sensitivity of central dopaminergic receptors which can be prevented by pretreatment with lithium.