AM630 ANTAGONISM OF CANNABINOID-STIMULATED [S-35] GTP-GAMMA-S BINDINGIN THE MOUSE-BRAIN

This research was designed to determine the action of the novel aminoa lkylindole AM630 (6-iodo-pravadoline) at the cannabinoid receptor by s tudying its interaction with the cannabinoid receptor agonist WIN 55,2 12-2 3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)methanone mesylate) on g uanosine-5'-O-(3-[S-35]thio)triphosphate ([S-35]GTP gamma S) binding i n mouse brain. WIN 55,212-2 stimulated [S-35]GTP gamma S binding, whil e AM630 had no effect. AM630 antagonized WIN 55,212-2-induced [S-35]GT P gamma S binding and shifted the WIN 55,212-2 dose-response curve to the right. These results clearly demonstrate that AM630 exerts cannabi noid receptor antagonist properties in the brain. (C) 1997 Elsevier Sc ience B.V.