Agent for improving motor complications or psychiatric symptoms in parkinson's disease

A technology for Parkinson's disease and complications, which is applied in the field of pharmaceuticals for improving motor complications or psychiatric symptoms of Parkinson's disease, and can solve problems such as a great impact on the quality of life of patients

Inactive Publication Date: 2010-08-18
DAIICHI SANKYO CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to the treatment guidelines of the Japanese Society of Neurology, when hallucinations appear, the principle is to stop the anti-Parkinson's disease drugs that have been used for treatment in turn, simplify the prescription, and finally try to treat with levodopa only. In the case of reduced doses, non-stereotype antipsychotics can be used in small amounts ("Japanese Society of Neurology Treatment Guidelines Parkinson's Disease Treatment Guidelines 2002", Ad Hoc Committee, Clinical Neurology, 2002, 42, p.430-94), but at the same time Point out the side effects of non-stereotypical antipsychotics, which have a great impact on the patient's quality of life due to the difficult control of Parkinson's disease symptoms

Method used

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  • Agent for improving motor complications or psychiatric symptoms in parkinson's disease
  • Agent for improving motor complications or psychiatric symptoms in parkinson's disease
  • Agent for improving motor complications or psychiatric symptoms in parkinson's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0109] Embodiment 1: For human 5-hydroxytryptamine 1A receptor, human dopamine D2L receptor, human dopa Binding affinity test for amine D2S receptor and human dopamine D3 receptor

[0110] 1-1. Binding affinity test for human serotonin 1A receptor

[0111] In the test, membrane samples prepared from Chinese hamster ovary (CHO-K1) cells expressing human serotonin 1A receptor were used. containing 5mM CaCl 2 , 0.1% ascorbic acid and 10μg / mL saponin in 50mM Tris-HCl (pH 7.4) buffer, add [ 3 H] 8-hydroxyl-2-(di-n-propylamino) tetralin ([ 3 H]8-OH-DPAT) (final concentration 1nM), test substance solution and membrane specimen. After the reaction solution was reacted at 25°C for 60 minutes, the reaction solution was filtered with a cell harvester, the filtered filter paper was transferred to a measuring bottle, a liquid scintillation agent was added, and a liquid scintillation counter was used to measure the residue on the filter paper. Receptor binding radioactivity. Nons...

Embodiment 2

[0133] Embodiment 2: To human 5-hydroxytryptamine 1A receptor, human dopamine D2L receptor, human dopamine Agonist and antagonist test of D2S receptor and human dopamine D3 receptor

[0134] Chinese hamster ovary (CHO-K1) cells expressing human serotonin 1A receptors, Chinese hamster ovary (CHO) cells expressing human dopamine D2L receptors, Chinese hamster ovary (CHO) cells expressing human dopamine D2S receptors were used in the experiment. ) cells and membrane samples prepared from Chinese hamster ovary (CHO) cells expressing human dopamine D3 receptor. In the agonist test, for 5-hydroxytryptamine 1A receptors, to containing 100mM NaCl, 3mM MgCl 2 and 10μg / mL saponin in 20mM Hepes-NaOH (pH 7.4) buffer solution, add [ 35 S] GTPγS (final concentration 0.1 nM), GDP solution (final concentration 3 μM), test substance solution, and membrane sample were reacted at 25° C. for 30 minutes. In addition, for dopamine (D2L, D2S and D3) receptors, add 100mM NaCl, 10mM MgCl 2 , 1m...

Embodiment 3

[0145] Embodiment 3: Adenylyl cyclase inhibition test by means of rat serotonin 1A receptor (complete Full agonist and partial agonist discrimination test)

[0146] In Example 3, 8-OH-DPAT and {2-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-1,2-benzothiazole-3(2H)- Acetone 1,1-dioxide} (hereinafter referred to as ipsapirone for comparison. 8-OH-DPAT is known as a representative serotonin 1A receptor full agonist, and ipsapirone as a representative serotonin 1A receptor partial agonist.

[0147] Wistar male rats (9-15 weeks old) provided by Shimizu Laboratory Materials Co., Ltd. were used in the test. The head of the rat was cut off, and the hippocampus was quickly removed. Homogenization was performed in 10 times the amount of buffer (25 mM Tris-HCl, 1 mM EGTA, 5 mM EDTA, 5 mM DTT, 300 mM sucrose, 100 KIU / ml aprotinin, pH 7.4). Centrifuge at 500×g, 4°C for 5 minutes, then centrifuge the supernatant at 39,000×g, 4°C for 10 minutes, and prepare the precipitate as a rat hippo...

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Abstract

It is intended to provide an agent for improving motor complications accompanying levodopa treatment of Parkinson's disease, delaying the onset of motor complications accompanying levodopa treatment, and inhibiting or delaying the progression of symptoms of Parkinson's disease, comprising a compound represented by the formula (I): a pharmacologically acceptable salt thereof or a hydrate thereof. The compound of the formula (I) has serotonin 1A receptor partial agonistic activity and also has a dopamine D3 receptor agonistic activity without having a dopamine D2 receptor antagonistic activity, has an effect of improving and delaying the onset of motor complications accompanying the repetitive administration of levodopa, and is effective also in accompanying psychiatric symptoms in patients with advanced-stage Parkinson's disease.

Description

technical field [0001] The present invention relates to methods for improving the motor complications accompanying the treatment of Parkinson's disease with levodopa, delaying the onset of motor complications accompanying the treatment with levodopa, and inhibiting or delaying the development of symptoms of Parkinson's disease potion. The present invention also relates to an agent for improving the psychiatric symptoms accompanying the progression of Parkinson's disease. Background technique [0002] Parkinson's disease is a neurodegenerative disease whose main symptoms are resting tremor, rigidity, akinesia, and disorder of postual reflex. Parkinson's disease is divided into two types: early-onset Parkinson's disease and progressive Parkinson's disease. That is, early Parkinson's disease refers to an earlier onset condition without use of levodopa and dopamine receptor agonists; while advanced Parkinson's disease refers to those who have taken levodopa and have developed ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/553A61K31/198A61K45/00A61P25/14A61P25/16A61P43/00C07D413/14
CPCC07D413/14A61K31/198A61K31/553A61K45/06A61P25/14A61P25/16A61P25/22A61P25/24A61P43/00A61K2300/00
Inventor 谷吉弘小山诚
Owner DAIICHI SANKYO CO LTD
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