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Use of nicotinic acetylcholine receptor alpha 7 activators

A kind of use, free base technology, applied in the field of use of nicotinic acetylcholine receptor α7 activator, can solve problems such as side effects and involuntary movement

Pending Publication Date: 2019-07-26
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, for many patients, long-term dopamine agonist therapy causes involuntary movements (dyskinesias), a significant side effect (review: Fabbrini et al., Movement Disorders, 2007, 22(10), 1379-1389; Konitsiotis, Expert Opin Investig Drugs, 2005, 14(4), 377-392; Brown et al., IDrugs, 2002, 5(5), 454-468)

Method used

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  • Use of nicotinic acetylcholine receptor alpha 7 activators
  • Use of nicotinic acetylcholine receptor alpha 7 activators
  • Use of nicotinic acetylcholine receptor alpha 7 activators

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0437] The usefulness of α7-nAChR agonists or α7-nAChR positive allosteric modulators in the treatment of the above-mentioned disorders can be demonstrated by a series of standard experiments including those set forth below.

[0438] 1. In vitro experiments

[0439] 1.1. Selectivity of selected α7-nAChR agonists to α4β2-nAChR

[0440] From the activity / selectivity data presented below, it was concluded that the compounds are selective agonists of the α7-nAChR.

[0441]

[0442] detection : To assess the activity of α7-nAChR, a functional assay was used using GH3 cells recombinantly expressing human α7-nAChR. 72 hours before the experiment, 50,000 cells / well were seeded in a black 96-well plate (Costar) and incubated at 37°C in a humid atmosphere (5% CO 2 / 95% air). On the day of the experiment, tap the culture plate to discard the culture medium, and replace it with 100 μl growth medium containing 2 mM Fluo-4 (Molecular Probes) and 2.5 mM probenecid (Sigma). Cells...

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Abstract

The invention concerns the use of a nicotinic acetylcholine receptor alpha 7 activators, and in particular to the use of the nicotinic acetylcholine receptor alpha 7 activators for the treatment, prevention or delay of progression of dyskinesia associated with dopamine agonist therapy in Parkinson's Disease.

Description

[0001] This application is a divisional application of PCT application PCT / EP2010 / 063946 filed on September 22, 2010, with the title of invention "Use of Nicotinic Acetylcholine Receptor α7 Activator", the date when said PCT application entered the Chinese national phase dated March 22, 2012, with application number 201080042255.4. technical field [0002] The present invention relates to the pharmaceutical use of nicotinic acetylcholine receptor α7 (α7-nAChR) activators, ie α7-nAChR agonists or positive allosteric modulators. Background technique [0003] Parkinson's disease (PD) is a chronic and progressive degenerative disorder of the central nervous system that often impairs patients' motor skills and language abilities. The hallmarks of Parkinson's disease are variable and include one or more of the following: tremor, rigidity, bradykinesia, akinesia, disturbances in gait and posture, postural instability, disturbances in speech and swallowing, and cognitive impairment ...

Claims

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Application Information

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IPC IPC(8): A61K31/444A61K31/198A61P25/14A61P25/16
CPCA61K31/198A61K45/06A61P25/14A61P25/16A61P43/00A61K2300/00
Inventor T·迪保罗D·费尔巴哈B·戈麦斯-曼西利亚D·约翰斯
Owner NOVARTIS AG
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