Rilmazafone

Jcl Sprague-Dawley (adult male, 7-8 weeks old)^[1]

200 mg/kg (5-day pretreatment + single dose); 600 mg/kg (3-day pretreatment + 200 mg/kg single dose); 200 mg/kg (single dose, liver collection); 600 mg/kg (3-day pretreatment)

p.o.; daily for 3 days; daily for 5 days; single dose

Showed plasma levels of metabolite M-1 similar to controls at peak but undetectable by 4 hours post-dose, M-2 plus M-D peaked at 2 hours then decreased rapidly, and M-3 plus M-A peaked between 2-4 hours then decreased rapidly in rats pretreated with 200 mg/kg daily for 5 days followed by 200 mg/kg single dose.
Showed peak plasma levels of all measured metabolites (M-1, M-2 plus M-D, M-3 plus M-A) significantly lower than controls, with M-1 peaking at 15-60 minutes, M-2 plus M-D peaking at 1 hour, and M-3 plus M-A peaking at 2 hours, all declining rapidly thereafter in rats pretreated with 600 mg/kg daily for 3 days followed by 200 mg/kg single dose.
Suppressed hepatic 7-methoxycoumarin O-demethylase activity to 45.1 nmol/min/g liver, a statistically significant reduction compared to controls in rats given a single 200 mg/kg dose with liver collection at 6 hours.
Increased hepatic 7-methoxycoumarin O-demethylase activity to 130.7 nmol/min/g liver, 7-ethoxycoumarin O-deethylase activity to 220.8 nmol/min/g liver, and 7-propoxycoumarin O-depropylase activity to 175.7 nmol/min/g liver, all statistically significant increases compared to controls in rats given 600 mg/kg daily for 3 days.

Wistar rats (male, 240-320 g, sleep disturbance model)^[2]

0.3, 1, 3 mg/kg

p.o.; single dose

Shortened sleep latency to 51.6 min (1 mg/kg) and 48.0 min (3 mg/kg), respectively, compared to control.
Decreased awake time to 198.0 min and increased non-REM sleep time to 139.0 min at 3 mg/kg compared to control.
Showed no significant effects on sleep latency, awake time, or non-REM sleep time at 0.3 mg/kg compared to control.
Caused no significant effects on total REM sleep time at all tested doses compared to control.