Effects of GR203040, an NK1 antagonist, on radiation- and cisplatin-induced tissue damage in the ferret.
1. The effects of GR203040, a tachykinin neurokinin1 receptor antagonist, on tissue damage induced by X-irradiation (Rad) or cisplatin (Cisp) were investigated in ferrets. 2. GR203040 (0.3 mg/kg SC) reduced the Rad-induced plasma protein extravasation (PPE) in the duodenum and kidney by 25% in each tissue. 3. GR203040 (3 mg/kg SC, 5-min pretreatment and every 8 hr for 48 hr after Cisp) reduced the Cisp-induced PPE in the duodenum, jejunum and lung by 59, 52 and 60%, respectively. 4. Histological examination showed that GR203040 also ameliorated the Rad- and Cisp-induced tissue damage.
Alfieri
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AB
Systems Biology Research Unit, Glaxo Wellcome Research & Development, Medicines Research Centre, Stevenage, Hertfordshire, United Kingdom.
Gardner
C J
CJ
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000633:toxicity*; D002199:Capillary Permeability / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000633:toxicity*; D004386:Duodenum / Q000098:blood supply / Q000187:drug effects / Q000528:radiation effects; D005289:Ferrets; D006651:Histocytochemistry; D007583:Jejunum / Q000098:blood supply / Q000187:drug effects / Q000528:radiation effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000528:radiation effects; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*; D001743:Urinary Bladder / Q000098:blood supply / Q000187:drug effects / Q000528:radiation effects; D014916:Whole-Body Irradiation
D000932:Antiemetics; D000970:Antineoplastic Agents; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D013777:Tetrazoles; C097591:(2-methoxy-5-tetrazol-1-ylbenzyl)(2-phenylpiperidin-3-yl)amine; D002945:Cisplatin