Zatosetron maleate(LY 277359 maleate) is a potent and selective serotonin 5HT3 receptor antagonist for the study of acute migraine.

Acute administration of Zatosetron maleate at doses of 0.1 mg/kg (n=21) and 0.3 mg/kg (n=5) significantly reduces the activity of A10 dopamine cells in male rats, an effect not observed with doses of 0.01, 0.05, 1.0, or 10 mg/kg or with saline administration. The reduction in active A10 dopamine cells begins 60 minutes post-intraperitoneal (i.p.) administration at 0.1 mg/kg, with significant decreases observed at 60-90 minutes (0.65±0.11, P=0.03, n=5), deepening at 90-120 minutes (0.53±0.08, P=0.004, n=5), and stabilizing from 2 to 3 hours (0.50±0.05, P=0.0004, n=5). Single-unit recordings reveal that intravenous (i.v.) administration of Zatosetron maleate inhibits A10 dopamine cell activity with an ED50 of 0.12 mg/kg (n=8). Chronic administration at 0.1 mg/kg (n=16) also leads to a significant decrease in active A10 dopamine cells, with no significant effect at doses of 0.01, 1.0, or 10 mg/kg or with saline (n=4, 8, 7, and 5, respectively).