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Weiyi Ong - One of the best experts on this subject based on the ideXlab platform.
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role of prefrontal cortical calcium independent phospholipase a2 in antinociceptive effect of the norepinephrine reuptake inhibitor antidepresssant Maprotiline
Neuroscience, 2017Co-Authors: Weesiong Chew, Markus R. Wenk, Sukumaran Shalini, Federico Torta, Christian S Stohler, Deron R Herr, J F Yeo, Weiyi OngAbstract:The prefrontal cortex is essential for executive functions such as decision-making and planning. There is also accumulating evidence that it is important for the modulation of pain. In this study, we investigated a possible role of prefrontal cortical calcium-independent phospholipase A2 (iPLA2) in antinociception induced by the norepinephrine reuptake inhibitor (NRI) and tetracyclic (tricyclic) antidepressant, Maprotiline. Intraperitoneal injections of Maprotiline increased iPLA2 mRNA and protein expression in the prefrontal cortex. This treatment also reduced grooming responses to von-Frey hair stimulation of the face after facial carrageenan injection, indicating decreased sensitivity to pain. The antinociceptive effect of Maprotiline was abrogated by iPLA2 antisense oligonucleotide injection to the prefrontal cortex, indicating a role of this enzyme in antinociception. In contrast, injection of iPLA2 antisense oligonucleotide to the somatosensory cortex did not reduce the antinociceptive effect of Maprotiline. Lipidomic analysis of the prefrontal cortex showed decrease in phosphatidylcholine species, but increase in lysophosphatidylcholine species, indicating increased PLA2 activity, and release of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) after Maprotiline treatment. Differences in sphingomyelin/ceramide were also detected. These changes were not observed in Maprotiline-treated mice that received iPLA2 antisense oligonucleotide to the prefrontal cortex. Metabolites of DHA and EPA may help to strengthen a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate a role of prefrontal cortical iPLA2 and its enzymatic products in the antinociceptive effect of Maprotiline.
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Role of prefrontal cortical calcium independent phospholipase A2 in antidepressant-like effect of Maprotiline
The International Journal of Neuropsychopharmacology, 2011Co-Authors: Lynette Hui-wen Lee, Chay Hoon Tan, Guanghou Shui, Markus R. Wenk, Weiyi OngAbstract:There is increasing interest in the pathophysiology and neurochemistry of the prefrontal cortex (PFC) in depression. Blood flow and metabolism are decreased in the PFC of patients with depression compared to controls. Changes in long-chain polyunsaturated fatty acids (PUFAs) are also associated with depression. This study was conducted to elucidate a possible role of PFC activity of an enzyme involved in the release of docosahexaenoic acid (DHA), i.e. calcium-independent phospholipase A2 (iPLA2), in the effects of the norepinephrine reuptake inhibitor (NRI) antidepressant, Maprotiline, in mice. Treatment of Balb/C mice with Maprotiline for 4 wk resulted in reduction in the level of behavioural despair, as determined by decreased immobility and increased climbing during the forced swim test. In contrast, mice treated with Maprotiline plus bilateral prefrontal cortical injections of antisense oligonucleotide to iPLA2, showed significantly increased immobility and decreased climbing, to levels comparable to saline-treated controls, indicating abolishment of the antidepressant-like effect of Maprotiline. Lipidomic analyses showed significant decreases in phosphatidylcholine species containing long-chain PUFAs and increases in lysophosphatidylcholine after Maprotiline treatment, indicating increased PLA2 activity and endogenous release of eicosapentaenoic acid (EPA) or DHA after Maprotiline treatment. These changes in lipid profiles were absent in mice that received Maprotiline and PFC injections of antisense oligonucleotide to iPLA2. Together, the results indicate that PFC iPLA2 activity plays an important role in the antidepressant-like effect of Maprotiline, possibly through endogenous release of long-chain PUFAs.
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changes in ampa subunit expression in the mouse brain after chronic treatment with the antidepressant Maprotiline a link between noradrenergic and glutamatergic function
Experimental Brain Research, 2006Co-Authors: Chay Hoon Tan, Jun Yang, Weiyi OngAbstract:Potentiation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function has been proposed as being useful in the treatment of depression, but thus far, little is known about the possible changes in AMPA receptor expression in the brain, after antidepressant treatment. The present study was carried out to study the expression of AMPA receptor subunits in different brain regions of mice that had been chronically injected with Maprotiline. The latter is a modified tricyclic antidepressant that functions as a noradrenaline uptake inhibitor. Daily intraperitoneal injection with 10 mg/kg Maprotiline for 30 days resulted in significantly increased GluR1 and GluR2/3 subunit expression in the nucleus accumbens and dorsal striatum as detected by immunohistochemistry; and significantly increased GluR1 and GluR2/3 expression in the hippocampus, as demonstrated by Western blot analysis. No change, or a decrease in GluR2 expression was detected in all the brain regions by both immunohistochemistry and Western blots. The increase in GluR1 and GluR2/3, but no increase in GluR2 subunits suggests that there could be an increase in calcium permeability of AMPA receptors in limbic/striatal brain regions after Maprotiline treatment. This could lead to increased synaptic activity or plasticity in the hippocampus and striatum, and may underlie the therapeutic effect of maprotline, and possibly, other antidepressant drugs.
Hansjurgen Moller - One of the best experts on this subject based on the ideXlab platform.
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plasma concentrations of fluvoxamine and Maprotiline in major depression implications on therapeutic efficacy and side effects
European Neuropsychopharmacology, 1993Co-Authors: Siegfried Kasper, A Vieira, Hermes Andreas Kick, Markus Dotsch, Hansjurgen MollerAbstract:Abstract We examined the relationship between plasma concentrations of specific acting antidepressants (fluvoxamine/Maprotiline) and clinical improvement as well as the impact of the magnitude of the plasma concentration of these antidepressants on side effects. Patients (32 patients with major depression) were treated within a double-blind parallel trial for four weeks and plasma concentrations were obtained before, on days 8 and 28 of the trial. Although there was a fixed-flexible dosage design it was apparent that 16 patients (89%) of the fluvoxamine group and all patients of the Maprotiline group received a dosage between 200 and 300 mg/day in the last week of the trial. Plasma concentrations (mean ± SD μg/l) of fluvoxamine were 125 ± 91 and 142 ± 108 on days 8 and 28, respectively and the range of fluvoxamine plasma concentrations on day 28 was from 20 to 417 μg/l. Plasma concentrations (mean ± SD μg/l) of Maprotiline were 146 ± 62 and 202 ± 134 on days 8 and 28, respectively and the range of Maprotiline plasma concentration on day 28 was from 12 to 428 μg/l. There was no linear relationship between plasma concentrations of both antidepressants (fluvoxamine/Maprotiline) and oral dosage. Whereas there was no correlation between fluvoxamine concentration and clinical response there was a tendency that higher Maprotiline concentrations were associated with a better antidepressive efficacy at the end of the trial. Higher concentrations of fluvoxamine as well as of Maprotiline were significantly (P
Stephen Metcalfe - One of the best experts on this subject based on the ideXlab platform.
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gender differences in the efficacy of fluoxetine and Maprotiline in depressed patients a double blind trial of antidepressants with serotonergic or norepinephrinergic reuptake inhibition profile
European Neuropsychopharmacology, 2001Co-Authors: Ferenc Martenyi, Martin Dossenbach, Karin Mraz, Stephen MetcalfeAbstract:Background: Depression has emerged as a contrastive area of gender differences in psychiatry, as epidemiological data has consistently shown depression is twice as common in women as men. The pharmacodynamic effect of antidepressants may also show gender differences, as suggested by reports of better response of young women to non-tricyclic antidepressants. Methods: The antidepressive effect of an SSRI (fluoxetine) and a tetracyclic antidepressant with selective norepinephrine reuptake inhibitory effect (Maprotiline) was compared in a 6-week, double-blind trial of 105 depressed patients. Results: No significant difference was observed in the change of HAMD17 total score from baseline to week 6 between fluoxetine- and Maprotiline-treated patients. A significant difference was observed in females (fluoxetine, −17.8; Maprotiline, −13.9; P=0.017) between treatment groups, but not in males. Amongst females, the difference was significant in women aged <44 years (fluoxetine, −18.4; Maprotiline, −12.9; P=0.023) but not ≥44 years. Conclusions: Females in their reproductive period are more responsive to SSRI (fluoxetine) than norepinephrinergic tetracyclic antidepressant (Maprotiline) treatment. Normal cyclical ovulation, and estrogen release may have a clinically relevant pharmacodynamic interaction with serotonergic antidepressants.
Chay Hoon Tan - One of the best experts on this subject based on the ideXlab platform.
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Role of prefrontal cortical calcium independent phospholipase A2 in antidepressant-like effect of Maprotiline
The International Journal of Neuropsychopharmacology, 2011Co-Authors: Lynette Hui-wen Lee, Chay Hoon Tan, Guanghou Shui, Markus R. Wenk, Weiyi OngAbstract:There is increasing interest in the pathophysiology and neurochemistry of the prefrontal cortex (PFC) in depression. Blood flow and metabolism are decreased in the PFC of patients with depression compared to controls. Changes in long-chain polyunsaturated fatty acids (PUFAs) are also associated with depression. This study was conducted to elucidate a possible role of PFC activity of an enzyme involved in the release of docosahexaenoic acid (DHA), i.e. calcium-independent phospholipase A2 (iPLA2), in the effects of the norepinephrine reuptake inhibitor (NRI) antidepressant, Maprotiline, in mice. Treatment of Balb/C mice with Maprotiline for 4 wk resulted in reduction in the level of behavioural despair, as determined by decreased immobility and increased climbing during the forced swim test. In contrast, mice treated with Maprotiline plus bilateral prefrontal cortical injections of antisense oligonucleotide to iPLA2, showed significantly increased immobility and decreased climbing, to levels comparable to saline-treated controls, indicating abolishment of the antidepressant-like effect of Maprotiline. Lipidomic analyses showed significant decreases in phosphatidylcholine species containing long-chain PUFAs and increases in lysophosphatidylcholine after Maprotiline treatment, indicating increased PLA2 activity and endogenous release of eicosapentaenoic acid (EPA) or DHA after Maprotiline treatment. These changes in lipid profiles were absent in mice that received Maprotiline and PFC injections of antisense oligonucleotide to iPLA2. Together, the results indicate that PFC iPLA2 activity plays an important role in the antidepressant-like effect of Maprotiline, possibly through endogenous release of long-chain PUFAs.
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changes in ampa subunit expression in the mouse brain after chronic treatment with the antidepressant Maprotiline a link between noradrenergic and glutamatergic function
Experimental Brain Research, 2006Co-Authors: Chay Hoon Tan, Jun Yang, Weiyi OngAbstract:Potentiation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function has been proposed as being useful in the treatment of depression, but thus far, little is known about the possible changes in AMPA receptor expression in the brain, after antidepressant treatment. The present study was carried out to study the expression of AMPA receptor subunits in different brain regions of mice that had been chronically injected with Maprotiline. The latter is a modified tricyclic antidepressant that functions as a noradrenaline uptake inhibitor. Daily intraperitoneal injection with 10 mg/kg Maprotiline for 30 days resulted in significantly increased GluR1 and GluR2/3 subunit expression in the nucleus accumbens and dorsal striatum as detected by immunohistochemistry; and significantly increased GluR1 and GluR2/3 expression in the hippocampus, as demonstrated by Western blot analysis. No change, or a decrease in GluR2 expression was detected in all the brain regions by both immunohistochemistry and Western blots. The increase in GluR1 and GluR2/3, but no increase in GluR2 subunits suggests that there could be an increase in calcium permeability of AMPA receptors in limbic/striatal brain regions after Maprotiline treatment. This could lead to increased synaptic activity or plasticity in the hippocampus and striatum, and may underlie the therapeutic effect of maprotline, and possibly, other antidepressant drugs.
Deron R Herr - One of the best experts on this subject based on the ideXlab platform.
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role of prefrontal cortical calcium independent phospholipase a2 in antinociceptive effect of the norepinephrine reuptake inhibitor antidepresssant Maprotiline
Neuroscience, 2017Co-Authors: Weesiong Chew, Markus R. Wenk, Sukumaran Shalini, Federico Torta, Christian S Stohler, Deron R HerrAbstract:Abstract The prefrontal cortex is essential for executive functions such as decision-making and planning. There is also accumulating evidence that it is important for the modulation of pain. In this study, we investigated a possible role of prefrontal cortical calcium-independent phospholipase A 2 (iPLA 2 ) in antinociception induced by the norepinephrine reuptake inhibitor (NRI) and tetracyclic (tricyclic) antidepressant, Maprotiline. Intraperitoneal injections of Maprotiline increased iPLA 2 mRNA and protein expression in the prefrontal cortex. This treatment also reduced grooming responses to von-Frey hair stimulation of the face after facial carrageenan injection, indicating decreased sensitivity to pain. The antinociceptive effect of Maprotiline was abrogated by iPLA 2 antisense oligonucleotide injection to the prefrontal cortex, indicating a role of this enzyme in antinociception. In contrast, injection of iPLA 2 antisense oligonucleotide to the somatosensory cortex did not reduce the antinociceptive effect of Maprotiline. Lipidomic analysis of the prefrontal cortex showed decrease in phosphatidylcholine species, but increase in lysophosphatidylcholine species, indicating increased PLA2 activity, and release of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) after Maprotiline treatment. Differences in sphingomyelin/ceramide were also detected. These changes were not observed in Maprotiline-treated mice that received iPLA 2 antisense oligonucleotide to the prefrontal cortex. Metabolites of DHA and EPA may help to strengthen a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate a role of prefrontal cortical iPLA 2 and its enzymatic products in the antinociceptive effect of Maprotiline.
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role of prefrontal cortical calcium independent phospholipase a2 in antinociceptive effect of the norepinephrine reuptake inhibitor antidepresssant Maprotiline
Neuroscience, 2017Co-Authors: Weesiong Chew, Markus R. Wenk, Sukumaran Shalini, Federico Torta, Christian S Stohler, Deron R Herr, J F Yeo, Weiyi OngAbstract:The prefrontal cortex is essential for executive functions such as decision-making and planning. There is also accumulating evidence that it is important for the modulation of pain. In this study, we investigated a possible role of prefrontal cortical calcium-independent phospholipase A2 (iPLA2) in antinociception induced by the norepinephrine reuptake inhibitor (NRI) and tetracyclic (tricyclic) antidepressant, Maprotiline. Intraperitoneal injections of Maprotiline increased iPLA2 mRNA and protein expression in the prefrontal cortex. This treatment also reduced grooming responses to von-Frey hair stimulation of the face after facial carrageenan injection, indicating decreased sensitivity to pain. The antinociceptive effect of Maprotiline was abrogated by iPLA2 antisense oligonucleotide injection to the prefrontal cortex, indicating a role of this enzyme in antinociception. In contrast, injection of iPLA2 antisense oligonucleotide to the somatosensory cortex did not reduce the antinociceptive effect of Maprotiline. Lipidomic analysis of the prefrontal cortex showed decrease in phosphatidylcholine species, but increase in lysophosphatidylcholine species, indicating increased PLA2 activity, and release of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) after Maprotiline treatment. Differences in sphingomyelin/ceramide were also detected. These changes were not observed in Maprotiline-treated mice that received iPLA2 antisense oligonucleotide to the prefrontal cortex. Metabolites of DHA and EPA may help to strengthen a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate a role of prefrontal cortical iPLA2 and its enzymatic products in the antinociceptive effect of Maprotiline.