(±)-Fabesetron hydrochloride

Mice and Rats^[1]
Male Sprague-Dawley rats weighing 220 to 330 g and male ddy mice weighing 25 to 35 g are used. (±)-Fabesetron, Ondansetron, Granisetron, Methysergide, Ketanserin and Atropine are dissolved in distilled water. 5-HT, 2-methyl-5-HT, 1-phenylbiguanide and 5-MeOT are dissolved in physiological saline. Diazepam is suspended with 0.5% methylcellulose solution. The drugs are administered to rats at a volume of 2 mL/ kg and to mice at a volume of 5 mL/kg.
Dogs^[2]
Beagle dogs of either sex weighting 8.0 to18.5 kg are used in the study. Dogs are injected i.v. with MTX (2.5 mg/kg/mL) at 7:30 AM. The animal behavior is recorded using a video camera with an automatic night photographing system for up to 72 h and analyzed at the end of the experiment. (±)-Fabesetron (1 and 3.2 mg/kg), Ondansetron (1 mg/kg), Tropisetron (1 mg/kg), CP-122,721 (0.1 mg/kg), or vehicle (0.5 mL/kg) is administered i.v. at 24, 36, 48, and 60 h after MTX treatment. Episodes of emesis occurring within a few minutes are defined as a single emetic episode. A 12 h artificial light cycle (lights on between 7:30 AM and 7:30 PM) is used throughout the study. Dogs are given a standard laboratory dog chow (300 g/day) and water ad libitum. The animals are retested with MTX at least 6 weeks later.

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