Table 5. Tissue Distribution Studies Using Oral Dosing^a.

		protein binding (fu)c
no.	mGlu5 IC50 (nM)b	plasma	brain	total plasma (nM)	total brain (nM)	unbound plasma (nM)	unbound brain (nM)	Kpd	Kp,uue	unbound brain/mGlu5 IC50
27	11	0.106	0.078	3000	2580	318	201	0.86	0.63	18
28	3.1	0.015	0.011	2570	2870	38.6	31.6	1.1	0.82	10
33	33	0.081	0.044	4820	3220	390	142	0.67	0.36	4.3

^aAverage n = 2, male Sprague–Dawley rats; dose = 10 mg/kg; vehicle = 10% polysorbate 80 in 0.5% methyl cellulose; t = 1 h post-dose.

^bCalcium mobilization mGlu₅ assay; values are an average of n ≥ 3 independent experiments.

^cf_u = Fraction unbound; equilibrium dialysis assay; brain = mouse brain homogenates.

^dK_p = total brain to total plasma ratio.

^eK_p,uu = unbound brain (brain f_u × total brain) to unbound plasma (plasma f_u × total plasma) ratio.