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

A Alfieri, C Gardner

Index: Gen. Pharmacol. 29(2) , 245-50, (1997)

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Abstract

1. The effect of the tachykinin neurokinin1 (NK1) receptor antagonist GR203040 on cyclophosphamide (CYP)-induced bladder damage was investigated in rats and ferrets. The 5-hydroxytryptamine3 receptor antagonists ondansetron and granisetron were similarly examined in ferrets. 2. In the rat, GR203040 (10 and 30 mg/kg i.p.) 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 (1 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.