The NK1 antagonist GR203040 inhibits cyclophosphamide-induced damage in the rat and ferret bladder.
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.
Alfieri
A
A
Systems Biology Research Unit, Glaxo Wellcome Research & Development, Medicines Research Centre, Stevenage, Hertfordshire, United Kingdom. CJG0872@GGR.CO.UK
Gardner
C
C
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005289:Ferrets; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*; D001743:Urinary Bladder / Q000033:anatomy & histology / Q000187:drug effects*
D001798:Blood Proteins; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D013777:Tetrazoles; C097591:(2-methoxy-5-tetrazol-1-ylbenzyl)(2-phenylpiperidin-3-yl)amine; D003520:Cyclophosphamide