Table 1

Summary of NK1 antagonist in vitro affinity and ex vivo binding potency in gerbil striatum and in vivo behavioral potency

Compound	K_i	IC₅₀	GFT EC₅₀	GFT EC₉₀	% Receptor Occupancy at EC₉₀
	nM	mg/kg
L-742,694	0.018	0.28	0.12	0.3	45
L-760,735-F	0.197	0.15	0.25	1	80
MK-869	0.070	0.43	0.06	1	65
GR205171	0.016	1.25	0.29	1	45
L-733,060	0.083	1.14	2.06	10	90
CP-122,721	0.035	7.61	2.09	10	60
CP-99994	0.145	36.8	10.6	30	40
L-733,061	165	>30	>30

The IC₅₀ column refers to the dose of antagonist that inhibited¹²⁵I-SP binding 50% ex vivo. The EC₅₀ for gerbil foot tapping represents the dose at which 50% inhibition of the behavioral response occurs. The GFT EC₉₀ is the dose of antagonist at which the response is almost maximally inhibited. Receptor occupancy at the GFT EC₉₀ was estimated by extrapolating from this dose to the intercept on the appropriate ex vivo binding inhibition curve then calculating the percentage of inhibition of ex vivo ¹²⁵I-SP binding as a measure of receptor occupancy (see text for details).