The NK1 antagonist GR203040 inhibits cyclophosphamide-induced damage in the rat and ferret bladder

1. The effect of the tachykinin neurokinin(1) (NK1) receptor antagonist GR203040 on cyclophosphamide (CYP)-induced bladder damage was investigated in rats and ferrets. The 5-hydroxy-tryptamine(3) receptor antagonists ondansetron and granisetron were similarly examined in ferrets. 2. In the rat, GR203040 (10 and 30 mg/kg IF) reduced the CYP-induced plasma protein extravasation in the bladder by 44% and 73%, respectively (P<0.05 and 0.005; cf. CYP controls); in the ferret, a 57% reduction (P<0.005) was observed after GR203040 (0.3 mg/kg SC). No decrease was observed in ferrets with either ondansetron or granisetron (I mg/kg SC). 3. GR203040 attenuated the CYP induced damage in the rat and ferret bladder, at the same dose in the ferret previously shown to inhibit CYP-induced emesis. GEN PHARMAC 29;2:245-250, 1997. (C) 1997 Elsevier Science Inc.