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Review

Cannabinoid receptor agonists and antagonists

Pages 301-313 | Published online: 25 Feb 2005
 

Abstract

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 aminoalkylindoles developed by Sterling (WIN 55212-2 analogues), the fatty acid derivatives derived from the endogenous ligand anandamide, and Sanofi’s diaryl pyrazoles. Moreover, other compounds, such as benzofurans (Lilly) or substituted aromatic amide derivatives (Japan Tobacco) that 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 agonists (Merck, Sanofi) with potential applications as immunomodulants and the development of the first selective CB1 antagonist SR 141716, followed recently by the first CB2 antagonist SR 144528. Turning these newly discovered pharmacological tools into useful drugs remains the challenge for research in coming years.

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