CANNABINOID RECEPTOR AGONISTS AND ANTAGONISTS

Following the discovery of two distinct cannabinoid receptors (CB1 and CB2) in the early 1990s, the medicinal chemistry of cannabinoids has seen renewed interest. In the last decade, at least three entirely new chemical series were shown to bind to cannabinoid receptors: the amin oalkylindoles developed by Sterling (WIN 55212-2 analogues), the fatty acid derivatives derived from the endogenous ligand anandamide, and S anofi's diaryl pyrazoles. Moreover, other compounds, such as benzofura ns (Lilly) or substituted aromatic amide derivatives (Japan Tobacco) t hat also bind to cannabinoid receptor have recently been disclosed in the patent literature. In terms of pharmacological profile, the major advances of the last five years are the emergence of selective CB2 ago nists (Merck, Sanofi) with potential applications as immunomodulants a nd the development of the first selective CB1 antagonist SR 141716, fo llowed recently by the first CB2 antagonist SR 144528. Turning these n ewly discovered pharmacological tools into useful drugs remains the ch allenge for research in coming years.