The first CNS-active carborane: A novel P2X7 receptor antagonist with antidepressant activity

Shane M Wilkinson; Hendra Gunosewoyo; Melissa L Barron; Aurelie Boucher; Michelle McDonnell; Peter Turner; Daniel E Morrison; Maxwell R Bennett; Iain S McGregor; Louis M Rendina; Michael Kassiou

doi:10.1021/cn500054n

The first CNS-active carborane: A novel P2X7 receptor antagonist with antidepressant activity

ACS Chem Neurosci. 2014 May 21;5(5):335-9. doi: 10.1021/cn500054n. Epub 2014 Apr 3.

Authors

Shane M Wilkinson¹, Hendra Gunosewoyo, Melissa L Barron, Aurelie Boucher, Michelle McDonnell, Peter Turner, Daniel E Morrison, Maxwell R Bennett, Iain S McGregor, Louis M Rendina, Michael Kassiou

Affiliation

¹ School of Chemistry, ‡Faculty of Health Science, §Discipline of Pharmacology, and ∥School of Psychology, Sydney University , NSW 2006, Australia.

Abstract

Relative to other polycyclic frameworks (1-3), a carborane cage (4 and Cs·5) exerts a significant biological effect as an inhibitor of the purinergic P2X7 receptor (P2X7R) which allows one to target depression in vivo and thus demonstrate, for the first time, that a carborane has the capacity to modify CNS activity.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antidepressive Agents / chemistry
Antidepressive Agents / therapeutic use*
Central Nervous System / drug effects*
Central Nervous System / metabolism
Depression / drug therapy*
Humans
Polycyclic Compounds / chemistry
Polycyclic Compounds / therapeutic use*
Purinergic P2X Receptor Antagonists / therapeutic use*
Receptors, Purinergic P2X7 / metabolism*

Substances

Antidepressive Agents
Polycyclic Compounds
Purinergic P2X Receptor Antagonists
Receptors, Purinergic P2X7