TABLE 4

Activity of ADX71743 in the mouse MB test and measured plasma, CSF concentrations, and CSF concentration/IC₅₀ (in vitro) of ADX71743 in mice at the end of the MB experiment

CSF exposure was calculated from the plasma exposure using mice plasma protein binding (fu = 4.4%).

Treatment	Route	Dose	Animal	Marbles Buried	Change	Plasma Exposure		CSF Exposure		CSF/EC_{50 (In Vitro)}
		mg/kg	n	mean ± S.E.M.	%	ng/ml	nM	ng/ml	nM
CD	s.c.		10	6.3 ± 0.5
ADX71743	s.c.	50	10	2.4 ± 0.6^**	−62	3451	12,814	152	564	4
ADX71743	s.c.	100	10	2.7 ± 0.8^*	−57	6990	25,958	308	1142	9
ADX71743	s.c.	150	10	1.7 ± 0.7^***	−73	10,430	38,732	459	1704	14
Saline	p.o.		10	6.3 ± 0.9
Chlordiazepoxide	p.o.	10	10	2.3 ± 0.6^**	−63

↵* P < 0.01; **P < 0.05; and ***P < 0.001 compared with corresponding vehicle.