MORPHOLINOALKYLINDENES AS ANTINOCICEPTIVE AGENTS - NOVEL CANNABINOID RECEPTOR AGONISTS

Indene analogs of pravadoline exhibited antinociceptive activity in se veral animal models. The inhibition of prostaglandin (PG) synthesis in mouse brain microsomes was diminished in these pravadoline analogs, b ut they were potent in inhibiting electrically stimulated contractions in the mouse vas deferens (MVD) preparations. Binding studies with li gand WIN 55212-2 have aided to demonstrate that the morpholinoalkylind ene binding site is functionally equivalent with cannabinoid binding s ite. The antinociceptive activity of the indene derivatives appears to be mediated by increased affinity for the cannabinoid receptor.