The Experts below are selected from a list of 6903 Experts worldwide ranked by ideXlab platform
Yutaka Fukushima - One of the best experts on this subject based on the ideXlab platform.
-
Prediction of plasma concentrations of Mianserin and desmethylMianserin at steady state from those after an initial dose of Mianserin.
Therapeutic drug monitoring, 1993Co-Authors: Koichi Otani, Kazuo Mihara, Motohiro Okada, Osamu Tanaka, Sunao Kaneko, Yutaka FukushimaAbstract:The relationships between the plasma concentrations of Mianserin and desmethylMianserin at 18 h after initial dosing and those at steady state were studied in 19 depressed patients receiving 30 mg of Mianserin at bedtime. Significant linear relationships were observed for Mianserin, desmethylMianserin, and Mianserin plus desmethylMianserin. The present study thus suggests that the plasma concentrations of these compounds after an initial dose of Mianserin can be used for the prediction of an optimal dose
-
Subjective side effects of Mianserin in relation to plasma concentrations of Mianserin and desmethylMianserin.
Therapeutic drug monitoring, 1992Co-Authors: Koichi Otani, Sunao Kaneko, Hiroshi Sasa, Hisashi Higuchi, Yasuo Hishikawa, Yutaka FukushimaAbstract:The main purpose of the present study was to examine the possibility that plasma concentrations of Mianserin and its metabolite, desmethylMianserin, might be predicted by recording subjective side effects. In 44 depressed patients, subjective side effects during 3 weeks of treatment with 30 mg of Mianserin were evaluated by the UKU Side Effect Rating Scale, and their relationships to plasma concentrations of Mianserin and desmethylMianserin were analyzed. There was no significant relationship between plasma concentrations of these compounds and the occurrence of Mianserin-induced side effects, except for dryness of mouth during week one. Our study, therefore, suggests that it is difficult to predict plasma concentrations of Mianserin and desmethylMianserin based on the occurrence of subjective side effects.
-
Is there a therapeutic window for plasma concentration of Mianserin plus desmethylMianserin
Human Psychopharmacology: Clinical and Experimental, 1991Co-Authors: Koichi Otani, Sunao Kaneko, Hiroshi Sasa, Tsuyoshi Kondo, Yutaka FukushimaAbstract:The relationship between clinical effects and plasma concentrations of Mianserin and desmethylMianserin was studied in 29 cases of major depression during 3 weeks of Mianserin treatment. The daily dose of Mianserin was 30 mg in 27 cases and 20 mg in two cases. There was a significant U-shaped relationship between the final Montgomery Asberg Depression Rating Scale (MADRS) score and the steady-state plasma concentration of Mianserin (p
Sunao Kaneko - One of the best experts on this subject based on the ideXlab platform.
-
effects of thioridazine an inhibitor of cyp2d6 on the steady state plasma concentrations of the enantiomers of Mianserin and its active metabolite desmethylMianserin in depressed japanese patients
Pharmacogenetics, 1997Co-Authors: Norio Yasui, Gunnel Tybring, Koichi Otani, Kazuo Mihara, Akihito Suzuki, J O Svensson, Sunao KanekoAbstract:The antidepressant Mianserin is administered as a racemate of the S(+)- and R(-)-enantiomers. Previous in-vitro studies have suggested that CYP2D6 is involved in the stereoselective metabolism of Mianserin and its active metabolite, desmethylMianserin. To determine a role for CYP2D6 in vivo, the effects of thioridazine, an inhibitor of CYP2D6, on the steady-state plasma concentrations of the enantiomers of Mianserin and desmethylMianserin were examined in 13 depressed Japanese patients. All patients were taking 30 mg of racemic Mianserin at bedtime for 8-50 days. Thioridazine (40 mg/day) was coadministered for 1 week, and blood samplings were performed before and after thioridazine coadministration, 12 h after bedtime dosing. Plasma concentrations of the enantiomers of Mianserin and desmethylMianserin were measured by HPLC, and the CYP2D6 genotype was determined by allele-specific PCR analysis. Thioridazine significantly increased plasma concentration of S(+)-Mianserin (mean SD: 78.2 +/- 35.0 vs. 150.8 +/- 48.7 nM, P < 0.001), but not R(-)-Mianserin (39.8 +/- 21.2 vs. 39.5 +/- 20.6 nM, NS). Thioridazine also significantly increased plasma concentrations of both S-desmethylMianserin (11.9 +/- 2.8 vs. 24.4 +/- 10.7 nM, P < 0.01) and R-desmethylMianserin (42.6 +/- 28.4 vs. 115.6 +/- 36.9 nM, P < 0.001). One patient homozygous for the defective allele CYP2D6*5 had the second highest and highest plasma concentrations of S(+)-Mianserin and R-desmethylMianserin, respectively, before thioridazine coadministration, and exhibited little increase in plasma concentration of the drugs after thioridazine coadministration. These results suggest that thioridazine specifically inhibits the metabolism of S(+)-Mianserin and R-desmethylMianserin, probably through inhibition of CYP2D6, but not R(-)-Mianserin.
-
The CYP2D6 Genotype and Plasma Concentrations of Mianserin Enantiomers in Relation to Therapeutic Response to Mianserin in Depressed Japanese Patients
Journal of clinical psychopharmacology, 1997Co-Authors: Kazuo Mihara, Marja-liisa Dahl, Gunnel Tybring, Leif Bertilsson, Koichi Otani, Sunao KanekoAbstract:The relationship between therapeutic response to racemic Mianserin and steady-state plasma concentrations of S(+)- and R(-)-Mianserin was studied in 26 Japanese patients with major depression. The daily dose of Mianserin was 30 mg, and the duration of treatment was 3 weeks. Regarding S-Mianserin, th
-
Prediction of plasma concentrations of Mianserin and desmethylMianserin at steady state from those after an initial dose of Mianserin.
Therapeutic drug monitoring, 1993Co-Authors: Koichi Otani, Kazuo Mihara, Motohiro Okada, Osamu Tanaka, Sunao Kaneko, Yutaka FukushimaAbstract:The relationships between the plasma concentrations of Mianserin and desmethylMianserin at 18 h after initial dosing and those at steady state were studied in 19 depressed patients receiving 30 mg of Mianserin at bedtime. Significant linear relationships were observed for Mianserin, desmethylMianserin, and Mianserin plus desmethylMianserin. The present study thus suggests that the plasma concentrations of these compounds after an initial dose of Mianserin can be used for the prediction of an optimal dose
-
Subjective side effects of Mianserin in relation to plasma concentrations of Mianserin and desmethylMianserin.
Therapeutic drug monitoring, 1992Co-Authors: Koichi Otani, Sunao Kaneko, Hiroshi Sasa, Hisashi Higuchi, Yasuo Hishikawa, Yutaka FukushimaAbstract:The main purpose of the present study was to examine the possibility that plasma concentrations of Mianserin and its metabolite, desmethylMianserin, might be predicted by recording subjective side effects. In 44 depressed patients, subjective side effects during 3 weeks of treatment with 30 mg of Mianserin were evaluated by the UKU Side Effect Rating Scale, and their relationships to plasma concentrations of Mianserin and desmethylMianserin were analyzed. There was no significant relationship between plasma concentrations of these compounds and the occurrence of Mianserin-induced side effects, except for dryness of mouth during week one. Our study, therefore, suggests that it is difficult to predict plasma concentrations of Mianserin and desmethylMianserin based on the occurrence of subjective side effects.
-
Is there a therapeutic window for plasma concentration of Mianserin plus desmethylMianserin
Human Psychopharmacology: Clinical and Experimental, 1991Co-Authors: Koichi Otani, Sunao Kaneko, Hiroshi Sasa, Tsuyoshi Kondo, Yutaka FukushimaAbstract:The relationship between clinical effects and plasma concentrations of Mianserin and desmethylMianserin was studied in 29 cases of major depression during 3 weeks of Mianserin treatment. The daily dose of Mianserin was 30 mg in 27 cases and 20 mg in two cases. There was a significant U-shaped relationship between the final Montgomery Asberg Depression Rating Scale (MADRS) score and the steady-state plasma concentration of Mianserin (p
Koichi Otani - One of the best experts on this subject based on the ideXlab platform.
-
effects of thioridazine an inhibitor of cyp2d6 on the steady state plasma concentrations of the enantiomers of Mianserin and its active metabolite desmethylMianserin in depressed japanese patients
Pharmacogenetics, 1997Co-Authors: Norio Yasui, Gunnel Tybring, Koichi Otani, Kazuo Mihara, Akihito Suzuki, J O Svensson, Sunao KanekoAbstract:The antidepressant Mianserin is administered as a racemate of the S(+)- and R(-)-enantiomers. Previous in-vitro studies have suggested that CYP2D6 is involved in the stereoselective metabolism of Mianserin and its active metabolite, desmethylMianserin. To determine a role for CYP2D6 in vivo, the effects of thioridazine, an inhibitor of CYP2D6, on the steady-state plasma concentrations of the enantiomers of Mianserin and desmethylMianserin were examined in 13 depressed Japanese patients. All patients were taking 30 mg of racemic Mianserin at bedtime for 8-50 days. Thioridazine (40 mg/day) was coadministered for 1 week, and blood samplings were performed before and after thioridazine coadministration, 12 h after bedtime dosing. Plasma concentrations of the enantiomers of Mianserin and desmethylMianserin were measured by HPLC, and the CYP2D6 genotype was determined by allele-specific PCR analysis. Thioridazine significantly increased plasma concentration of S(+)-Mianserin (mean SD: 78.2 +/- 35.0 vs. 150.8 +/- 48.7 nM, P < 0.001), but not R(-)-Mianserin (39.8 +/- 21.2 vs. 39.5 +/- 20.6 nM, NS). Thioridazine also significantly increased plasma concentrations of both S-desmethylMianserin (11.9 +/- 2.8 vs. 24.4 +/- 10.7 nM, P < 0.01) and R-desmethylMianserin (42.6 +/- 28.4 vs. 115.6 +/- 36.9 nM, P < 0.001). One patient homozygous for the defective allele CYP2D6*5 had the second highest and highest plasma concentrations of S(+)-Mianserin and R-desmethylMianserin, respectively, before thioridazine coadministration, and exhibited little increase in plasma concentration of the drugs after thioridazine coadministration. These results suggest that thioridazine specifically inhibits the metabolism of S(+)-Mianserin and R-desmethylMianserin, probably through inhibition of CYP2D6, but not R(-)-Mianserin.
-
The CYP2D6 Genotype and Plasma Concentrations of Mianserin Enantiomers in Relation to Therapeutic Response to Mianserin in Depressed Japanese Patients
Journal of clinical psychopharmacology, 1997Co-Authors: Kazuo Mihara, Marja-liisa Dahl, Gunnel Tybring, Leif Bertilsson, Koichi Otani, Sunao KanekoAbstract:The relationship between therapeutic response to racemic Mianserin and steady-state plasma concentrations of S(+)- and R(-)-Mianserin was studied in 26 Japanese patients with major depression. The daily dose of Mianserin was 30 mg, and the duration of treatment was 3 weeks. Regarding S-Mianserin, th
-
Prediction of plasma concentrations of Mianserin and desmethylMianserin at steady state from those after an initial dose of Mianserin.
Therapeutic drug monitoring, 1993Co-Authors: Koichi Otani, Kazuo Mihara, Motohiro Okada, Osamu Tanaka, Sunao Kaneko, Yutaka FukushimaAbstract:The relationships between the plasma concentrations of Mianserin and desmethylMianserin at 18 h after initial dosing and those at steady state were studied in 19 depressed patients receiving 30 mg of Mianserin at bedtime. Significant linear relationships were observed for Mianserin, desmethylMianserin, and Mianserin plus desmethylMianserin. The present study thus suggests that the plasma concentrations of these compounds after an initial dose of Mianserin can be used for the prediction of an optimal dose
-
Subjective side effects of Mianserin in relation to plasma concentrations of Mianserin and desmethylMianserin.
Therapeutic drug monitoring, 1992Co-Authors: Koichi Otani, Sunao Kaneko, Hiroshi Sasa, Hisashi Higuchi, Yasuo Hishikawa, Yutaka FukushimaAbstract:The main purpose of the present study was to examine the possibility that plasma concentrations of Mianserin and its metabolite, desmethylMianserin, might be predicted by recording subjective side effects. In 44 depressed patients, subjective side effects during 3 weeks of treatment with 30 mg of Mianserin were evaluated by the UKU Side Effect Rating Scale, and their relationships to plasma concentrations of Mianserin and desmethylMianserin were analyzed. There was no significant relationship between plasma concentrations of these compounds and the occurrence of Mianserin-induced side effects, except for dryness of mouth during week one. Our study, therefore, suggests that it is difficult to predict plasma concentrations of Mianserin and desmethylMianserin based on the occurrence of subjective side effects.
-
Is there a therapeutic window for plasma concentration of Mianserin plus desmethylMianserin
Human Psychopharmacology: Clinical and Experimental, 1991Co-Authors: Koichi Otani, Sunao Kaneko, Hiroshi Sasa, Tsuyoshi Kondo, Yutaka FukushimaAbstract:The relationship between clinical effects and plasma concentrations of Mianserin and desmethylMianserin was studied in 29 cases of major depression during 3 weeks of Mianserin treatment. The daily dose of Mianserin was 30 mg in 27 cases and 20 mg in two cases. There was a significant U-shaped relationship between the final Montgomery Asberg Depression Rating Scale (MADRS) score and the steady-state plasma concentration of Mianserin (p
Paul Willner - One of the best experts on this subject based on the ideXlab platform.
-
stereospecific reversal of stress induced anhedonia by Mianserin and its enantiomer
Psychopharmacology, 1994Co-Authors: Survjit Cheeta, Chris L.e. Broekkamp, Paul WillnerAbstract:Chronic sequential exposure to a variety of mild unpredictable stressors has previously been found to depress the consumption of a dilute (1%) sucrose solution and to inhibit food-induced place preference conditioning. In the present study, using a simplified version of the mild stress procedure, the decreased sucrose intake was reversed by chronic (4 weeks) treatment with the atypical antidepressant Mianserin. The racemic compound (±)-Mianserin (5 mg/kg per day) and one of its enantiomers, (+)-Mianserin (2.5 mg/kg) were effective in this model; a lower dose of (±)-Mianserin (2.5 mg/kg), and the other enantiomer, (−)-Mianserin (2.5 mg/kg), were ineffective. Vehicle-treated stressed animals were also subsensitive to food reward in the place conditioning procedure: normal place preference conditioning was reinstated by chronic treatment with (±)-Mianserin (5 mg/kg) or (+)-Mianserin, but not by the lower dose of (±)-Mianserin (2.5 mg/kg) or by (−)-Mianserin. Raclopride (100 µg/kg) reinstated the decrease in sucrose intake in stressed animals successfully treated with (±)- or (+)-Mianserin. The results suggest that (+)-Mianserin is the active enantiomer in reversing chronic mild stress-induced anhedonia, and further support the hypothesis of a dopaminergic mechanism of antidepressant action in this paradigm.
-
Stereospecific reversal of stress-induced anhedonia by Mianserin and its (+)-enantiomer.
Psychopharmacology, 1994Co-Authors: Survjit Cheeta, Chris L.e. Broekkamp, Paul WillnerAbstract:Chronic sequential exposure to a variety of mild unpredictable stressors has previously been found to depress the consumption of a dilute (1%) sucrose solution and to inhibit food-induced place preference conditioning. In the present study, using a simplified version of the mild stress procedure, the decreased sucrose intake was reversed by chronic (4 weeks) treatment with the atypical antidepressant Mianserin. The racemic compound (±)-Mianserin (5 mg/kg per day) and one of its enantiomers, (+)-Mianserin (2.5 mg/kg) were effective in this model; a lower dose of (±)-Mianserin (2.5 mg/kg), and the other enantiomer, (−)-Mianserin (2.5 mg/kg), were ineffective. Vehicle-treated stressed animals were also subsensitive to food reward in the place conditioning procedure: normal place preference conditioning was reinstated by chronic treatment with (±)-Mianserin (5 mg/kg) or (+)-Mianserin, but not by the lower dose of (±)-Mianserin (2.5 mg/kg) or by (−)-Mianserin. Raclopride (100 µg/kg) reinstated the decrease in sucrose intake in stressed animals successfully treated with (±)- or (+)-Mianserin. The results suggest that (+)-Mianserin is the active enantiomer in reversing chronic mild stress-induced anhedonia, and further support the hypothesis of a dopaminergic mechanism of antidepressant action in this paradigm.
Survjit Cheeta - One of the best experts on this subject based on the ideXlab platform.
-
stereospecific reversal of stress induced anhedonia by Mianserin and its enantiomer
Psychopharmacology, 1994Co-Authors: Survjit Cheeta, Chris L.e. Broekkamp, Paul WillnerAbstract:Chronic sequential exposure to a variety of mild unpredictable stressors has previously been found to depress the consumption of a dilute (1%) sucrose solution and to inhibit food-induced place preference conditioning. In the present study, using a simplified version of the mild stress procedure, the decreased sucrose intake was reversed by chronic (4 weeks) treatment with the atypical antidepressant Mianserin. The racemic compound (±)-Mianserin (5 mg/kg per day) and one of its enantiomers, (+)-Mianserin (2.5 mg/kg) were effective in this model; a lower dose of (±)-Mianserin (2.5 mg/kg), and the other enantiomer, (−)-Mianserin (2.5 mg/kg), were ineffective. Vehicle-treated stressed animals were also subsensitive to food reward in the place conditioning procedure: normal place preference conditioning was reinstated by chronic treatment with (±)-Mianserin (5 mg/kg) or (+)-Mianserin, but not by the lower dose of (±)-Mianserin (2.5 mg/kg) or by (−)-Mianserin. Raclopride (100 µg/kg) reinstated the decrease in sucrose intake in stressed animals successfully treated with (±)- or (+)-Mianserin. The results suggest that (+)-Mianserin is the active enantiomer in reversing chronic mild stress-induced anhedonia, and further support the hypothesis of a dopaminergic mechanism of antidepressant action in this paradigm.
-
Stereospecific reversal of stress-induced anhedonia by Mianserin and its (+)-enantiomer.
Psychopharmacology, 1994Co-Authors: Survjit Cheeta, Chris L.e. Broekkamp, Paul WillnerAbstract:Chronic sequential exposure to a variety of mild unpredictable stressors has previously been found to depress the consumption of a dilute (1%) sucrose solution and to inhibit food-induced place preference conditioning. In the present study, using a simplified version of the mild stress procedure, the decreased sucrose intake was reversed by chronic (4 weeks) treatment with the atypical antidepressant Mianserin. The racemic compound (±)-Mianserin (5 mg/kg per day) and one of its enantiomers, (+)-Mianserin (2.5 mg/kg) were effective in this model; a lower dose of (±)-Mianserin (2.5 mg/kg), and the other enantiomer, (−)-Mianserin (2.5 mg/kg), were ineffective. Vehicle-treated stressed animals were also subsensitive to food reward in the place conditioning procedure: normal place preference conditioning was reinstated by chronic treatment with (±)-Mianserin (5 mg/kg) or (+)-Mianserin, but not by the lower dose of (±)-Mianserin (2.5 mg/kg) or by (−)-Mianserin. Raclopride (100 µg/kg) reinstated the decrease in sucrose intake in stressed animals successfully treated with (±)- or (+)-Mianserin. The results suggest that (+)-Mianserin is the active enantiomer in reversing chronic mild stress-induced anhedonia, and further support the hypothesis of a dopaminergic mechanism of antidepressant action in this paradigm.