Current Pharmaceutical Design - Volume 6, Issue 13, 2000

Research leading to the isolation of the plant cannabinoids during the 1960s and to the endogenous cannabinoids, during the 1990s is described. Investigations on two non-psychotropic, synthetic cannabinoids, HU-211, a neuroprotective agent and HU-308, a specific CB 2 agonist are presented.

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-methoxyindole (L768242) and 2-methyl-1-propyl-3-(1-naphthoyl)indole (JWH-015) have high affinity for the CB2 rece Read More

The acid metabolites of THC were discovered almost 30 years ago and were later shown to posses modest analgesic and anti-inflammatory activity in a variety of models. Ajulemic acid (CT3) is a more potent analog of THC-11-oic acid in which a dimethylheptyl side chain is substituted for the pentyl side chain of the naturally occurring metabolite. It produces analgesia in the mouse hot plate, the PPQ writhing, the formalin and Read More

Unlike natural cannabinoids which belong to the 6aR - trans series, the synthetic dexanabinol (HU-211), a 6aS-trans enantiomer, does not have affinity toward cannabinoid receptors and is devoid of cannabimimetic activity. On the other hand, dexanabinol demonstrated significant neuroprotective properties which prompted its development as a therapeutic agent. We now present the extension of a series of 6aS-tr Read More

The possible therapeutic use of marijuanas active principles, the cannabinoids, is currently being debated. It is now known that these substances exert several of their pharmacological actions by activating specific cell membrane receptors, the CB 1 and CB 2 cannabinoid receptor subtypes. This knowledge led to the design of synthetic cannabinoid agonists and antagonists with high therapeutic potential. The recent discovery Read More

The identification of arachidonylethanolamide (anandamide, AEA) as an endogenous cannabinoid has been an important development in cannabinoid research which has led to the identification of two proteins associated with cannabinoid physiology in addition to the CB1 and CB2 receptors. These proteins are anandamide amidohydrolase (AAH), an enzyme responsible for the hydrolytic breakdown of anandamide Read More