Anavex Life Sciences Corp (AVXL)

[F1ash]

A2-73 ~66% mouse at 10 mg/kg

Donepezil 93% rat at 10 mg/kg


PET data shows S1R occupancy is dose-dependent for ANAVEX®2-73 with a plateau at 68% ± 11% in whole brain


https://www.anavex.com/wp-content/uploads/2018/07/AAIC_2018-PET_Anavex_Final.pdf

Figure 1. Static image of PET scan of ANAVEX®2-73 in mouse at time 15-20 minutes at the following drug doses: A = WT control, B = 1 mg/kg ANAVEX®2-73, C = 10 mg/kg ANAVEX®2-73 and D = 30 mg/kg ANAVEX®2-73.
Table 1. This table summarizes binding potential and distribution volume values calculated using 2TCM and the calculated percent receptor occupancy.
1 mg/kg ANAVEX®2-73 0.81 ± 0.11 13.6 ± 2.1 20.8 ± 10.8
10 mg/kg ANAVEX®2-73 0.34 ± 0.09 7.9 ± 1.8

66.7 ± 9.1

30 mg/kg ANAVEX®2-73 0.32 ± 0.11 8.2 ± 1.8 68.3 ± 10.6 1 mg/kg PRE-084 0.93 ± 0.19 14.6 ± 1.5 8.4 ± 18.5



https://rd.springer.com/article/10.1007%2Fs00213-014-3533-2

Dose-dependent sigma-1 receptor occupancy by donepezil in rat brain can be assessed with 11C-SA4503 and microPET

RO increased dose-dependently and was 93 % at 10 mg/kg. ED50 was 1.29 mg/kg.