Table 2. Potency of GSK598809 in Occupying Brain D₃Rs in Rat, Baboon, and Human (comparison with GSK598809 affinity for D₃Rs).

	Potency as total concentration			Potency as free concentration		Affinity for D3R
	OCt,plasma50(ng/ml)	OCt,blood50(ng/ml)	OCt,brain50(ng/g)	OCu,blood50(nM)	OCu,brain50(nM)	Ki (nM)
Rat	23a	15	47	1.2b	2.3c	1.5
Baboon	36	ND	ND	ND	ND	ND
Human	66	41d	ND	3.9e	ND	6.2
Human (predicted)	87f	54g	NA	NA	NA	NA

Abbreviations: NA, not applicable; ND, not determined. As explained in Materials and Methods, OC₅₀^t,blood and OC₅₀^t,brain values in rat were determined by fitting the occupancy measured in the AcbSh vs the total concentration in the blood or brain, respectively; in human and baboon, the OC₅₀^t,plasma values were determined by simultaneous fitting of the occupancy measured in VST, GB ,and SN vs the total concentration in the plasma, during which the OC₅₀^t,plasma was considered a shared parameter.

^aCalculated from the rat OC₅₀^t,blood, adjusting for the blood/plasma ratio in rat (0.65).

^bCalculated from the rat OC₅₀^t,blood, adjusting for the f_u in rat blood (3.93) and the molecular weight (MW; 481.52 g/mol).

^cCalculated from the rat OC₅₀^t,brain, adjusting for the f_u in rat brain (2.33) and the MW.

^dCalculated from the human OC₅₀^t,plasma, adjusting for the blood/plasma ratio in human (0.62).

^eCalculated from the human OC₅₀^t,blood, adjusting for the f_u in human blood (4.55) and the MW.

^fCalculated from the human OC₅₀^t,blood (predicted), adjusting for the blood/plasma ratio in human (0.62).

^gPredicted from rat experimental data as explained in Materials and Methods.