Setipafant

Piglets^[1]
Male and female newborn piglets weighing 1550±31 g are used in all experiments. Six groups are studied. Group U₄ is the nonsurgical control group (n=15). No anesthesia is given. Animals are entrusted to their mother and killed at D₄. Group S is the sham control group (n=15). At D2 animals undergo laparotomy, intestinal exteriorization, and manipulation for 10 minutes before reintroduction to the abdominal cavity. They are killed at D4. Group I₄ consist of animals (n=15) in which ischemia surgery is performed at D2, and animals are killed at D4. Group IT₄ consist of animals (n=15) treated as in I₄ together with treatment with Setipafant (BN 50727), a PAF receptor antagonist, orally (50 mg/kg of body weight) the day before and daily after surgery until death, and intraperitoneally (50 mg/kg) during surgery. Group I₉ consisted of animals (n=15) in which ischemia surgery is performed at D2, and animals are killed at D9. Group IT₉ consist of animals (n=15) undergoing the same procedure as in Is together with treatment with Setipafant as in IT₄. Another group, U₉, is made up of control animals (n=15) that are used only for weight and blood sample studies at D9.
Rats^[2]
Male, Wistar rats weighing 160-205 g are used. Between 09 h 00 min and 10 h 00 min each day the animals are given an intraperitoneal injection of the PAF receptor antagonists, BN 52021 (10 mg/kg) or BN 50727(1 mg/kg), or their vehicle, and 30 min later they receive a subcutaneous injection of Dexamethasone sodium phosphate or vehicle. The effectiveness of BN 52021 and BN 50727 treatments is tested in preliminary experiments in anaesthetized (Inactin, 100 mg/kg, i.p.) male rats by injecting 25 and 50 ng/kg PAF into the right femoral vein 30 min before and 30 min after administration of either BN 52021, 10 mg/kg, i.p., or BN 50727, 1 mg/kg, i.p. Mean arterial blood pressure is monitored through a catheter inserted into the right femoral artery by an electromanometer using a Statham P23 dB pressure transducer.

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