title: 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.affiliation: Department of General Pharmacology, Pfizer Inc., Groton, CT 06340, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gonsalves
authors.forename: J
authors.initials: J
authors.lastname: Watson
authors.forename: C
authors.initials: C
authors.lastname: Ashton
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology* / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects; D019327:Copper Sulfate / Q000009:adverse effects; D004639:Emetics / Q000009:adverse effects; D005289:Ferrets; D007486:Ipecac / Q000009:adverse effects; D008139:Loperamide / Q000009:adverse effects; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D013237:Stereoisomerism; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D000932:Antiemetics; D004639:Emetics; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D008139:Loperamide; D007486:Ipecac; D019327:Copper Sulfate; D002945:Cisplatin; C099414:(2S,3S)-2-phenyl-3-((5-trifluoromethoxy-2-methoxy)benzylamino)piperidine