TABLE 3

Mavoglurant, dipraglurant and basimglurant mGlu₅ RO and exposure

Compound/Species	Oral Dose	Ligand for RO	mGlu₅ RO Means ± S.D.	Plasma Means ± S.D.	Brain Means ± S.D.
	Rat: mg/kg Human: mg		%	ng/ml	ng/ml
Mavoglurant/rat^a	3	[³H]M-MPEP	45 ± 4	128 ± 64.2	204 ± 78.5
	10		73 ± 2	466 ± 178.4	641 ± 178.4
	30		83 ± 3	1002 ± 612.7	1505 ± 234.8
Basimglurant/rat	N/A	[³H]ABP688	50^b	4.8^b	8.2^c
Basimglurant/human	0.5	[¹¹C]RO511232^c	25^d	4.20^e	7.2^f
Basimglurant/human	1.5	[¹¹C]RO511232^c	53^d	12.1^e	20.5^f
Dipraglurant/human	100	[¹⁸F]FPEB	27 ± 9.0^g	1586^h	174ⁱ
	200		44 ± 23^g	3172^h	349ⁱ
	300		54 ± 30^g	4758^h	523ⁱ

↵^a Values calculated from measured concentration (micromoles) presented in Bennett et al. (2014).
↵^b Quoted EC₅₀ (Lindemann et al., 2015).
↵^c Estimated based on Kp 1.7 (Lindemann et al., 2015).
↵^d Quoted at Css (Quiroz et al., 2016; PET study clinical trials.gov NCT01483469).
↵^e Estimated from day 1 concentration (Cosson et al., 2018) taking account of accumulation to Css.
↵^f Estimated at Css, assuming same brain partitioning as for rat.
↵^g Addex Therapeutics Initiating Report Life Science Capital July 19, 2016.
↵^h From normalizing day 1 50 mg human plasma C_max reported (793 ng/ml) Tison et al. (2016). Data consistent with reported plasma EC₅₀ 2910 ± 152 ng/ml (Wong et al., 2018).
↵ⁱ Brain estimated assuming same brain partitioning as measured in the rat (Kp 0.11).