Enantiospecific inhibition of emesis induced by nicotine in the house musk shrew (Suncus murinus) by the neurokinin1 (NK1) receptor antagonist CP-99,994.
Effects of the NK1 receptor antagonist CP-99,994 on nicotine-induced emesis were examined in Suncus murinus. CP-99,994 (3 and 10 mg/kg i.p.) attenuated emesis to (-)nicotine (4 mg/kg s.c.). CP-100,263 (3 and 10 mg/kg i.p.), the enantiomer of CP-99,994 with 1000 fold lower affinity for the NK1 receptor was without effect and RP67580 reduced emesis only at a dose of 30 mg/kg i.p. Responses to NK1 antagonists were ranked according to their affinities for the Suncus murinus NK1 receptor.
Tattersall
F D
FD
Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Essex, UK.
Rycroft
W
W
Marmont
N
N
Cascieri
M
M
Hill
R G
RG
Hargreaves
R J
RJ
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D009020:Morphine / Q000494:pharmacology; D015288:Neurokinin A / Q000037:antagonists & inhibitors*; D009538:Nicotine; D010880:Piperidines / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D012788:Shrews; D013237:Stereoisomerism; D013373:Substance P / Q000037:antagonists & inhibitors; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D007211:Indoles; D054833:Isoindoles; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; D009538:Nicotine; D009020:Morphine; D015288:Neurokinin A