The search for selective ligands
for the CB2 receptor

Huffman JW
Howard L. Hunter Chemistry Laboratory,
Clemson University,
Box 341905, Clemson,
South Carolina 29634-1905, USA.
Curr Pharm Des 2000 Sep; 6(13):1323-37


Following the identification of the CB2 receptor several groups explored the development of selective ligands for this receptor which occurs principally in the periphery. This led to the discovery that two cannabimimetic indoles, 1-(2, 3-dichlorobenzoyl)-2-methyl-3-(2-[1-morpholino]ethyl)-5-methoxyind ole (L768242) and 2-methyl-1-propyl-3-(1-naphthoyl)indole (JWH-015) have high affinity for the CB2 receptor with low affinity for the CB1 receptor. Shortly thereafter two 1-methoxy-delta8-THC analogues, 1-methoxy-delta8-THC-DMH (L759633) and 1-methoxy-delta9(11)-THC-DMH (L759656), were also found to have high affinity for the CB2 receptor and very little affinity for the CB1 receptor. Almost simultaneously two 1-deoxy-delta8-THC analogues, 1-deoxy-11-hydroxy-delta8-THC-DMH (JWH-051) and 1-deoxy-delta8-THC-DMH (JWH-057) were reported to have high affinity for the CB1 receptor, but even greater affinity for the CB2 receptor. These discoveries gave rise to a concerted effort by Huffman and co-workers to explore the structure-activity relationships (SAR) at CB2 of cannabimimetic indoles and 1-deoxy-delta8-THC analogues. These efforts have resulted in the synthesis and pharmacological evaluation of a number of derivatives of 3-(1-naphthoyl)indoles and 1-deoxy-delta8-THC analogues with various side chains. This review will describe the current status of the results of these studies and discuss the SAR for both these classes of ligands.

Hemp oil
Swiss hemp
Hemp seeds
Tolerant mice
Just say know
Cannabis: effects
Forgetful rodents
Stoned as a newt?
Stoned chocaholics?
The nectar of delight
Charas versus bhang

01 02 03 04 05 06 07 08 09 10 11 12 13 14 15


Future Opioids
BLTC Research
Utopian Pharmacology
The Hedonistic Imperative
When Is It Best To Take Crack Cocaine?

swan image
The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family