The development of cannabinoid antagonists

The discovery of two distinct cannabinoid receptors (CB1 and CB2) in the ea rly 1990's has revived the research on cannabinoid antagonists. While the s earch for antagonists based on the structure of agonists (classical cannabi noids or aminoalkylindoles) appeared rather disappointing, the first potent cannabinoid antagonists were developed in a new chemical series: the diary lpyrazoles. Since its discovery in 1994, the selective CB1 antagonist SR 14 1716 has became a major pharmacological tool to elucidate the physiological role of the CB1 cannabinoid receptor and its endogenous ligand. The select ive CB2 antagonist SR 144528 is expected to play the same role for the CB2 receptors, while the recent development of cannabinoid antagonists belongin g to other chemical series illustrates the interest of these compounds whic h are now considered as interesting therapeutic targets by many pharmaceuti cal companies.