Binding mode prediction of conformationally restricted anandamide analogs within the CB1 receptor

Table 1 Structures and affinity and relative efficacy data for the conformationally restricted anandamide analogs

Compound	Binding affinity, K_i(nM)	GTPγS binding	Adenylyl cyclase
CP55244	0.11	Strong stimulation	Strong inhibition
Anandamide	17	Strong stimulation	Strong inhibition
	38	Strong stimulation	Strong inhibition
	59	Moderate stimulation	Weak stimulation
	305	Moderate stimulation	Weak stimulation
	335	Strong stimulation	Moderate Inhibition
	371	Moderate stimulation	Weak stimulation
	4960	No change	Strong inhibition

Anandamide analogs were selected from a series of compounds developed and tested as reported previously [13]. Binding affinity was determined by the ability to compete for [³H]-CP55940 binding in rat brain membranes, G-protein activation was determined by the ability to stimulate [³⁵S]-GTPγS binding to G-proteins in rat brain membranes, and effector activity was determined by the ability to regulate adenylyl cyclase activity (inhibit through Gi or stimulate through Gs) in purified membranes from N18TG2 cells.