Figure 3.

Mouse receptor occupancy and MOG-EAE experiments with PIPE-359 (21i). (A) Dose–response receptor occupancy 2 h after po dose. [³H]-Pirenzepine (300 nM) was added ex vivo as a radiotracer. Occupancy was measured as % response of hM₁R-selective antagonist muscarinic toxin 7 (MT7)³¹ added ex vivo (300 nM). (B) Receptor occupancy time course of PIPE-359 at 30 mg/kg po. (C) Prophylactic treatment (qd 30 mg/kg po) with PIPE-359 in MOG-EAE performed in C57BL/6 mice (n = 10–15/group). EAE induction was performed on day 0 followed by once daily administration (qd) of PIPE-359 at 30 mg/kg po or vehicle for 21 days. Clinical scores were recorded daily, and changes were observed starting on day 6 and continued through day 22. ****, p < 0.0001 based on Sidak’s multiple comparison tests respective to vehicle controls.