The Experts below are selected from a list of 29934 Experts worldwide ranked by ideXlab platform
Hiroyasu Shiraishi - One of the best experts on this subject based on the ideXlab platform.
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Dopamine D1 and D2 receptor agents and their interaction influence the synaptic density of the rat prefrontal cortex
Neuroscience letters, 1999Co-Authors: Makoto Sugahara, Hiroyasu ShiraishiAbstract:Recent findings indicate that some monoamines contribute to synaptic maintenance. We examined the synaptic density of the prefrontal cortex of rats with the single or combined administration of D1 and D2 Antagonists and agonists. When each agent was administered individually, we observed a significant difference in synaptic density. This indicates that dopamine regulates synaptic maintenance. With the combined administration of Antagonists or agonists at high dosages, a synergistic effect was observed. With the combined administration of a D1 antagonist and D2 agonist or a D1 agonist and D2 antagonist, a low dose of the D2 receptor drug enhanced the effect of the D1 receptor drug. The D1 receptor drug offset the effect of the high dose of D2 receptor drug, suggesting the possibility that the D1 receptor family is essential for synaptic maintenance.
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Synaptic density of the prefrontal cortex regulated by dopamine instead of serotonin in rats.
Brain Research, 1998Co-Authors: Makoto Sugahara, Hiroyasu ShiraishiAbstract:Recent findings indicate that monoamine contributes to synaptic plasticity. We examined the synaptic density of the prefrontal cortex and parietal cortex of rats using dopamine (DA) Antagonists and agonists, as well as serotonin (5-HT) depleters and found a reduction in synaptic density in the prefrontal cortex lamina V–VI at a maximum of 20% with administration of a D1 antagonist (SCH23390) and at a maximum of 30% with a D2 antagonist (YM09151). Further, with the administration of D1+D2 Antagonists there was a 27% decrease in synaptic density, which was a larger reduction than the total of the single dosages of each DA antagonist at equal levels. Increase in synaptic density was seen at a maximum of 8.5% with dosage of a D1 agonist (SKF38390) and 14.5% with dosage of a D2 agonist (PPHT). The dosage of D1+D2 agonists showed a 27.1% increase in synaptic density. There was no change in synaptic density of the parietal cortex with either DA antagonist or agonist administration. Administration of 5-HT depleter pCPA resulted in a 13.8% reduction of synaptic density in the parietal cortex, though there was no change identified in the synaptic density in the prefrontal cortex. Based on these results, it was suggested that the area of the brain with affected synaptic plasticity could differ, depending on the type of monoamine.
Pat L. Needham - One of the best experts on this subject based on the ideXlab platform.
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n substituted 2 3 dihydro 1 4 benzodioxin 2 yl methylamine derivatives as D2 Antagonists 5 ht1a partial agonists with potential as atypical antipsychotic agents
Journal of Medicinal Chemistry, 1999Co-Authors: Alan Martin Birch, Paul Anthony Bradley, Julie C. Gill, Frank Kerrigan, Pat L. NeedhamAbstract:A series of N-substituted 1-(2,3-dihydro-1,4-benzodioxin-2-yl)methylamine derivatives with D2 antagonist/5-HT1A partial agonist activity has been prepared as potential atypical antipsychotic agents. Optimization of in vitro receptor binding activity and in vivo activity in rodent models of psychosis has led to compound 24, which showed good affinities for human D2, D3, and 5-HT1A receptors but significantly less affinity for human α1 adrenoceptors and rat H1 and muscarinic receptors. In rodents, 24 showed functional D2-like antagonism and 5-HT1A partial agonism. After oral dosing, 24 showed good activity in rodent antipsychotic tests and very little potential to cause extrapyramidal side effects (EPS), as measured by its ability to induce catalepsy in rats only at very high doses. In the light of this promising profile of activity, 24 has been selected for clinical investigation as a novel antipsychotic agent with a predicted low propensity to cause EPS.
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N-Substituted (2,3-Dihydro-1,4-benzodioxin-2-yl)methylamine Derivatives as D2 Antagonists/5-HT1A Partial Agonists with Potential as Atypical Antipsychotic Agents
Journal of Medicinal Chemistry, 1999Co-Authors: Alan Martin Birch, Paul Anthony Bradley, Julie C. Gill, Frank Kerrigan, Pat L. NeedhamAbstract:A series of N-substituted 1-(2,3-dihydro-1,4-benzodioxin-2-yl)methylamine derivatives with D2 antagonist/5-HT1A partial agonist activity has been prepared as potential atypical antipsychotic agents. Optimization of in vitro receptor binding activity and in vivo activity in rodent models of psychosis has led to compound 24, which showed good affinities for human D2, D3, and 5-HT1A receptors but significantly less affinity for human α1 adrenoceptors and rat H1 and muscarinic receptors. In rodents, 24 showed functional D2-like antagonism and 5-HT1A partial agonism. After oral dosing, 24 showed good activity in rodent antipsychotic tests and very little potential to cause extrapyramidal side effects (EPS), as measured by its ability to induce catalepsy in rats only at very high doses. In the light of this promising profile of activity, 24 has been selected for clinical investigation as a novel antipsychotic agent with a predicted low propensity to cause EPS.
Erkki Tolvanen - One of the best experts on this subject based on the ideXlab platform.
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zuclopenthixol a combined dopamine d1 D2 antagonist versus haloperidol a dopamine D2 antagonist in tardive dyskinesia
European Neuropsychopharmacology, 1991Co-Authors: Henrik Lublin, Jes Gerlach, Ulf Hagert, Birgit Meidahl, Cecilia Mølbjerg, Vagn Pederson, Claus Rendtorff, Erkki TolvanenAbstract:Animal data suggest that a D1 antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect. This has led to the hypothesis that neuroleptics with D1 antagonistic activity should cause a better suppression of tardive dyskinesia (TD) and less rebound aggravation after withdrawal than pure D2 Antagonists. In this study the effect of zuclopenthixol (mixed D1/D2 antagonist) and haloperidol (D2 antagonist) was evaluated in chronic psychotic patients with TD. Fifteen patients completed a randomized crossover study with blind evaluation of TD and parkinsonism. The test medications, haloperidol and zuclopenthixol, caused a significant suppression of TD and a significant increase of parkinsonism. No significant differences between haloperidol and zuclopenthixol were observed. No TD aggravation was seen. The lack of differences between the mixed D1/D2 antagonist and a D2 antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD.
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Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia
European Neuropsychopharmacology, 1991Co-Authors: Henrik Lublin, Jes Gerlach, Ulf Hagert, Birgit Meidahl, Cecilia Mølbjerg, Vagn Pederson, Claus Rendtorff, Erkki TolvanenAbstract:Animal data suggest that a D1 antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect. This has led to the hypothesis that neuroleptics with D1 antagonistic activity should cause a better suppression of tardive dyskinesia (TD) and less rebound aggravation after withdrawal than pure D2 Antagonists. In this study the effect of zuclopenthixol (mixed D1/D2 antagonist) and haloperidol (D2 antagonist) was evaluated in chronic psychotic patients with TD. Fifteen patients completed a randomized crossover study with blind evaluation of TD and parkinsonism. The test medications, haloperidol and zuclopenthixol, caused a significant suppression of TD and a significant increase of parkinsonism. No significant differences between haloperidol and zuclopenthixol were observed. No TD aggravation was seen. The lack of differences between the mixed D1/D2 antagonist and a D2 antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD.
Henrik Lublin - One of the best experts on this subject based on the ideXlab platform.
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Long-term treatment with low doses of the D1 antagonist NNC 756 and the D2 antagonist raclopride in monkeys previously exposed to dopamine Antagonists.
Psychopharmacology, 1994Co-Authors: Henrik Lublin, Jes Gerlach, Flemming MørkebergAbstract:EightCebus apella monkeys previously exposed to D1 and D2 Antagonists were treated subcutaneously for 8 weeks with the D1 antagonist NNC 756 (0.01mg/kg), followed by a wash-out period of 4 weeks and treatment with the D2 antagonist raclopride for 8 weeks (end doses 0.01 mg/kg). NNC 756 induced no dystonia, while marked dystonia was induced by raclopride. Mild tolerance to the dystonia-inducing effect of raclopride slowly developed. Both drugs induced significant sedation and mild bradykinesia. Sedation induced by NNC 756 was stronger than that of raclopride, while no differences were found regarding bradykinesia. The sedative effect of both NNC 756 and raclopride increased over time during chronic treatment. No changes in bradykinesia developed. No significant dyskinesia was induced by NNC 756, while raclopride significantly induced both acute and tardive oral dyskinesia. Furthermore, raclopride-induced acute dyskinesia worsened during chronic treatment. Concomitant treatment with NNC 756 tended to reduce the D1 agonist SKF 81297-induced dyskinesia and grooming, while concomitant treatment with raclopride increased SKF 81297-induced dyskinesia and tended to decrease SKF 81297-induced grooming. Chronic treatment with raclopride induced supersensitivity to both the D2/D3 agonist LY 171555 and SKF 81297, while chronic NNC 756 treatment only induced supersensitivity to SKF 81297. The findings indicate that D1 Antagonists may induce less dystonia and oral dyskinesia as compared with D2 Antagonists and support the hypothesis of both a permissive and an inhibitory interaction between D1 and D2 receptor systems.
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zuclopenthixol a combined dopamine d1 D2 antagonist versus haloperidol a dopamine D2 antagonist in tardive dyskinesia
European Neuropsychopharmacology, 1991Co-Authors: Henrik Lublin, Jes Gerlach, Ulf Hagert, Birgit Meidahl, Cecilia Mølbjerg, Vagn Pederson, Claus Rendtorff, Erkki TolvanenAbstract:Animal data suggest that a D1 antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect. This has led to the hypothesis that neuroleptics with D1 antagonistic activity should cause a better suppression of tardive dyskinesia (TD) and less rebound aggravation after withdrawal than pure D2 Antagonists. In this study the effect of zuclopenthixol (mixed D1/D2 antagonist) and haloperidol (D2 antagonist) was evaluated in chronic psychotic patients with TD. Fifteen patients completed a randomized crossover study with blind evaluation of TD and parkinsonism. The test medications, haloperidol and zuclopenthixol, caused a significant suppression of TD and a significant increase of parkinsonism. No significant differences between haloperidol and zuclopenthixol were observed. No TD aggravation was seen. The lack of differences between the mixed D1/D2 antagonist and a D2 antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD.
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Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia
European Neuropsychopharmacology, 1991Co-Authors: Henrik Lublin, Jes Gerlach, Ulf Hagert, Birgit Meidahl, Cecilia Mølbjerg, Vagn Pederson, Claus Rendtorff, Erkki TolvanenAbstract:Animal data suggest that a D1 antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect. This has led to the hypothesis that neuroleptics with D1 antagonistic activity should cause a better suppression of tardive dyskinesia (TD) and less rebound aggravation after withdrawal than pure D2 Antagonists. In this study the effect of zuclopenthixol (mixed D1/D2 antagonist) and haloperidol (D2 antagonist) was evaluated in chronic psychotic patients with TD. Fifteen patients completed a randomized crossover study with blind evaluation of TD and parkinsonism. The test medications, haloperidol and zuclopenthixol, caused a significant suppression of TD and a significant increase of parkinsonism. No significant differences between haloperidol and zuclopenthixol were observed. No TD aggravation was seen. The lack of differences between the mixed D1/D2 antagonist and a D2 antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD.
Makoto Sugahara - One of the best experts on this subject based on the ideXlab platform.
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Dopamine D1 and D2 receptor agents and their interaction influence the synaptic density of the rat prefrontal cortex
Neuroscience letters, 1999Co-Authors: Makoto Sugahara, Hiroyasu ShiraishiAbstract:Recent findings indicate that some monoamines contribute to synaptic maintenance. We examined the synaptic density of the prefrontal cortex of rats with the single or combined administration of D1 and D2 Antagonists and agonists. When each agent was administered individually, we observed a significant difference in synaptic density. This indicates that dopamine regulates synaptic maintenance. With the combined administration of Antagonists or agonists at high dosages, a synergistic effect was observed. With the combined administration of a D1 antagonist and D2 agonist or a D1 agonist and D2 antagonist, a low dose of the D2 receptor drug enhanced the effect of the D1 receptor drug. The D1 receptor drug offset the effect of the high dose of D2 receptor drug, suggesting the possibility that the D1 receptor family is essential for synaptic maintenance.
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Synaptic density of the prefrontal cortex regulated by dopamine instead of serotonin in rats.
Brain Research, 1998Co-Authors: Makoto Sugahara, Hiroyasu ShiraishiAbstract:Recent findings indicate that monoamine contributes to synaptic plasticity. We examined the synaptic density of the prefrontal cortex and parietal cortex of rats using dopamine (DA) Antagonists and agonists, as well as serotonin (5-HT) depleters and found a reduction in synaptic density in the prefrontal cortex lamina V–VI at a maximum of 20% with administration of a D1 antagonist (SCH23390) and at a maximum of 30% with a D2 antagonist (YM09151). Further, with the administration of D1+D2 Antagonists there was a 27% decrease in synaptic density, which was a larger reduction than the total of the single dosages of each DA antagonist at equal levels. Increase in synaptic density was seen at a maximum of 8.5% with dosage of a D1 agonist (SKF38390) and 14.5% with dosage of a D2 agonist (PPHT). The dosage of D1+D2 agonists showed a 27.1% increase in synaptic density. There was no change in synaptic density of the parietal cortex with either DA antagonist or agonist administration. Administration of 5-HT depleter pCPA resulted in a 13.8% reduction of synaptic density in the parietal cortex, though there was no change identified in the synaptic density in the prefrontal cortex. Based on these results, it was suggested that the area of the brain with affected synaptic plasticity could differ, depending on the type of monoamine.
