Use of compounds that selectively modulate astrocytic release of substances through hemichannels of connexins and pannexins, without influencing gap junctions, for the treatment of psychiatric disorders

Patent metadata

Field	Value
Publication number	US-9879058-B2
Application number	US-201314404358-A
Country	US
Kind code	B2
Filing date	May 31, 2013
Priority date	May 30, 2012
Publication date	Jan 30, 2018
Grant date	Jan 30, 2018

Abstract

The present invention is related to the use of compounds or pharmaceutically acceptable salts thereof that modulate astrocytic release of substances through connexin and pannexin hemichannels, for the treatment of psychiatric disorders. Compounds or pharmaceutically acceptable salts thereof used in the present invention comprise any compound that differentially modulates, blocks, opens, inhibits, and/or activates connexin and/or pannexin hemichannels from astrocytes while not affecting gap junctions. The invention is also related to a method for treating psychiatric disorders, comprising administering to a mammal or human a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, that modulates astrocytic release of substances through connexin and pannexin hemichannels. Pharmaceutical compositions and a screening method are also considered in the present invention. Examples are shown for connexin 43, connexin 30 and pannexin 1 hemichannel modulators shown not to affect gap junctions, in the form of both non peptide compounds and peptides which were tested in different models for psychiatric disorders, comprising PTSD, memory, anxiety and depression.

First claim

The invention claimed is:

1. A method of treating mood disorders comprising administering to a mammal or human a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, that modulates astrocytic release of substances through connexin 30 and connexin 43 hemichannels and pannexin hemichannels without influencing or disturbing the function of gap junctions wherein the compound is cacotheline: (2,3-Dihydro-4-nitro-2,3-dioxo-9,10-secostrychnidin-10-oic acid) or pharmaceutically acceptable salts thereof.

2. The method according to claim 1 , wherein the connexin hemichannels correspond to connexin 30 and connexin 43 hemichannels and the pannexin hemichannels correspond to pannexin 1 hemichannels.

3. The method according to claim 1 , wherein the compound differentially modulates, blocks, opens, inhibits, and/or activates connexin and/or pannexin hemichannels or a combination thereof from astrocytes while not affecting gap junctions directly.

4. The method according to claim 1 , wherein the compound interferes with functioning of connexins or pannexins or a combination thereof in their hemichannel configuration.

5. The method according to claim 4 , wherein the compound interferes with functioning of connexin 30 or connexin 43 or pannexin 1 or a combination thereof in their hemichannel configuration.

6. The method according to claim 2 , wherein the compound specifically affects connexin 43 or connexin 30 or pannexin 1 hemichannels or a combination thereof in the astrocytes without affecting gap junctions.

7. The method according to claim 2 , wherein the subjects to be treated with the method are human.

Assignees

• Univ Andres Bello
• Univ Gent
• Univ Leuven Kath
• Katholieke Univ Leuven Ku Leuven R & D

Inventors

• Stehberg Liberman Jimmy
• Leybaert Sinia Luc Gilbert
• Bultynck Demets Geert Albert
• Retamal Lucero Mauricio Antonio
• Gonzalez Nilo Fernando Danilo

Classifications

• A61P25/22

  Anxiolytics · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K14/78

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] · CPC title