Broad spectrum antiemetic effects of CP-122,721, a tachykinin NK1 receptor antagonist, in ferrets.

Abstract

The potent, selective, tachykinin NK1 receptor antagonist, CP-122,721 ([(+)-(2S,3S)-3-(2-methoxy-5-trifluoromethoxybenzyl)amino-2- phenylpiperidine]), at 0.01-1 mg/kg, s.c. reduced retching and vomiting elicited by loperamide, copper sulfate, ipecac syrup and cisplatin in a dose-dependent manner. ID50 values after subcutaneous administration ranged from 0.02 mg/kg (loperamide) to 0.08 mg/kg (ipecac). Oral CP-122,721 reduced cisplatin-induced emesis with an ID50 of approximately 0.08 mg/kg. The less active (2R, 3R)-enantiomer, CP-132.687, did not significantly suppress retching or vomiting induced by any of the emetogens. These data support the hypothesis that CP-122,721 blocks emesis by a specific action at tachykinin NK1 receptors. Its broad spectrum of antiemetic activity suggests a central site of action.

• Authors: S Gonsalves, J Watson, C Ashton
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 305 Issue 1-3 Pg. 181-5 (Jun 03 1996) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8813551 (Publication Type: Journal Article)

Chemical References

• Antiemetics
• Emetics
• Neurokinin-1 Receptor Antagonists
• Piperidines
• Loperamide
• Ipecac
• Copper Sulfate
• Cisplatin
• (2S,3S)-2-phenyl-3-((5-trifluoromethoxy-2-methoxy)benzylamino)piperidine

Topics

• Animals
• Antiemetics (pharmacology, therapeutic use)
• Cisplatin (adverse effects)
• Copper Sulfate (adverse effects)
• Emetics (adverse effects)
• Ferrets
• Ipecac (adverse effects)
• Loperamide (adverse effects)
• Male
• Neurokinin-1 Receptor Antagonists
• Piperidines (pharmacology, therapeutic use)
• Stereoisomerism
• Vomiting (chemically induced, drug therapy)