Latest advances in cannabinoid receptor agonists.
BACKGROUND
Since the discovery of cannabinoid receptors and their endogenous ligands in early 1990s, the endocannabinoid system has been shown to play a vital role in several pathophysiological processes. It has been targeted for the treatment of several diseases including neurodegenerative diseases (Parkinson's disease, Alzheimer's disease, Huntington's disease and MS), cancer, obesity, inflammatory bowel disease, neuropathic and inflammatory pain. The last decade has witnessed remarkable advances in the development of cannabinergic ligands displaying high selectivity and potency towards two subtypes of cannabinoid receptors, namely CB1 and CB2.


OBJECTIVE
In this review, we highlight the latest advances made in the development of cannabinoid agonists and summarize recently disclosed, novel chemical scaffolds as CB-selective agonists in patents that appeared during January 2008 - June 2009.


METHODS
Data presented here are obtained through the search of PubMed for research articles and reviews, and the website of European patents (http://ep.espacenet.com), SciFinder Scholar and US patents (www.uspto.gov).


CONCLUSIONS
Our analysis reveals prolific patenting activity mainly in the CB2 selective agonist area. Limiting the BBB penetrability, thereby, leading to peripherally restricted CB1/CB2 agonists and enhancing CB2-selectivity emerge as likely prerequisites for avoidance of adverse central CB1 mediated side effects.
Thakur
Ganesh A
GA
Northeastern University, Center for Drug Discovery, 116 Mugar Hall, Boston, MA 02115, USA. g.thakur@neu.edu
Tichkule
Ritesh
R
Bajaj
Shama
S
Makriyannis
Alexandros
A
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D008024:Ligands; D010330:Patents as Topic; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism
D063385:Cannabinoid Receptor Modulators; D008024:Ligands; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2