Compounds > 1-2-benzisothiazol-3(2h)-one--2-(4-(4-(7-chloro-2-3-dihydro-1-4-benzodioxin-5-yl)-1-piperazinyl)butyl)---1-1-dioxide

1-2-benzisothiazol-3(2h)-one--2-(4-(4-(7-chloro-2-3-dihydro-1-4-benzodioxin-5-yl)-1-piperazinyl)butyl)---1-1-dioxide and Depressive-Disorder--Major

1-2-benzisothiazol-3(2h)-one--2-(4-(4-(7-chloro-2-3-dihydro-1-4-benzodioxin-5-yl)-1-piperazinyl)butyl)---1-1-dioxide has been researched along with Depressive-Disorder--Major* in 1 studies

Trials

1 trial(s) available for 1-2-benzisothiazol-3(2h)-one--2-(4-(4-(7-chloro-2-3-dihydro-1-4-benzodioxin-5-yl)-1-piperazinyl)butyl)---1-1-dioxide and Depressive-Disorder--Major

Article	Year
Preclinical and clinical characterization of the selective 5-HT(1A) receptor antagonist DU-125530 for antidepressant treatment. British journal of pharmacology, 2012, Volume: 167, Issue:5 The antidepressant efficacy of selective 5-HT reuptake inhibitors (SSRI) and other 5-HT-enhancing drugs is compromised by a negative feedback mechanism involving 5-HT(1A) autoreceptor activation by the excess 5-HT produced by these drugs in the somatodendritic region of 5-HT neurones. 5-HT(1A) receptor antagonists augment antidepressant-like effects in rodents by preventing this negative feedback, and the mixed β-adrenoceptor/5-HT(1A) receptor antagonist pindolol improves clinical antidepressant effects by preferentially interacting with 5-HT(1A) autoreceptors. However, it is unclear whether 5-HT(1A) receptor antagonists not discriminating between pre- and post-synaptic 5-HT(1A) receptors would be clinically effective.. We characterized the pharmacological properties of the 5-HT(1A) receptor antagonist DU-125530 using receptor autoradiography, intracerebral microdialysis and electrophysiological recordings. Its capacity to accelerate/enhance the clinical effects of fluoxetine was assessed in a double-blind, randomized, 6 week placebo-controlled trial in 50 patients with major depression (clinicaltrials.gov identifier NCT01119430).. DU-125530 showed equal (low nM) potency to displace agonist and antagonist binding to pre- and post-synaptic 5-HT(1A) receptors in rat and human brain. It antagonized suppression of 5-hydroxytryptaminergic activity evoked by 8-OH-DPAT and SSRIs in vivo. DU-125530 augmented SSRI-induced increases in extracellular 5-HT as effectively as in mice lacking 5-HT(1A) receptors, indicating a silent, maximal occupancy of pre-synaptic 5-HT(1A) receptors at the dose used. However, DU-125530 addition to fluoxetine did not accelerate nor augment its antidepressant effects.. DU-125530 is an excellent pre- and post-synaptic 5-HT(1A) receptor antagonist. However, blockade of post-synaptic 5- HT(1A) receptors by DU-125530 cancels benefits obtained by enhancing pre-synaptic 5-hydroxytryptaminergic function. Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Adult; Animals; Antidepressive Agents; Brain; Depressive Disorder, Major; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Piperazines; Pyridines; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1A; Serotonin Antagonists; Serotonin Receptor Agonists; Thiazoles	2012

Article

Year

Preclinical and clinical characterization of the selective 5-HT(1A) receptor antagonist DU-125530 for antidepressant treatment.

British journal of pharmacology, 2012, Volume: 167, Issue:5

The antidepressant efficacy of selective 5-HT reuptake inhibitors (SSRI) and other 5-HT-enhancing drugs is compromised by a negative feedback mechanism involving 5-HT(1A) autoreceptor activation by the excess 5-HT produced by these drugs in the somatodendritic region of 5-HT neurones. 5-HT(1A) receptor antagonists augment antidepressant-like effects in rodents by preventing this negative feedback, and the mixed β-adrenoceptor/5-HT(1A) receptor antagonist pindolol improves clinical antidepressant effects by preferentially interacting with 5-HT(1A) autoreceptors. However, it is unclear whether 5-HT(1A) receptor antagonists not discriminating between pre- and post-synaptic 5-HT(1A) receptors would be clinically effective.. We characterized the pharmacological properties of the 5-HT(1A) receptor antagonist DU-125530 using receptor autoradiography, intracerebral microdialysis and electrophysiological recordings. Its capacity to accelerate/enhance the clinical effects of fluoxetine was assessed in a double-blind, randomized, 6 week placebo-controlled trial in 50 patients with major depression (clinicaltrials.gov identifier NCT01119430).. DU-125530 showed equal (low nM) potency to displace agonist and antagonist binding to pre- and post-synaptic 5-HT(1A) receptors in rat and human brain. It antagonized suppression of 5-hydroxytryptaminergic activity evoked by 8-OH-DPAT and SSRIs in vivo. DU-125530 augmented SSRI-induced increases in extracellular 5-HT as effectively as in mice lacking 5-HT(1A) receptors, indicating a silent, maximal occupancy of pre-synaptic 5-HT(1A) receptors at the dose used. However, DU-125530 addition to fluoxetine did not accelerate nor augment its antidepressant effects.. DU-125530 is an excellent pre- and post-synaptic 5-HT(1A) receptor antagonist. However, blockade of post-synaptic 5- HT(1A) receptors by DU-125530 cancels benefits obtained by enhancing pre-synaptic 5-hydroxytryptaminergic function.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Adult; Animals; Antidepressive Agents; Brain; Depressive Disorder, Major; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Piperazines; Pyridines; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1A; Serotonin Antagonists; Serotonin Receptor Agonists; Thiazoles

2012