Studies for the emetic mechanisms of ipecac syrup (TJN-119) and its active components in ferrets: involvement of 5-hydroxytryptamine receptors.
Ipecac syrup, prepared from a galentical ipecac, contains the nauseant alkaloids cephaeline and emetine. The involvement of receptors and serotonin- and dopamine-metabolizing enzymes in the emesis induced by ipecac syrup and these components was investigated. 1) In ferrets, the selective 5-HT3-receptor antagonist ondansetron (0.5 mg/kg, p.o.) prevented each emesis induced by TJN-119 (0.5 mL/kg, p.o.), cephaeline (0.5 mg/kg, p.o.) and emetine (5.0 mg/kg, p.o.), but the intraperitoneal administration of the selective dopamine D2-receptor antagonist sulpiride failed to significantly suppress the TJN-119, cephaeline and emetine-induced emesis at a dose of 0.1 mg/kg that blocked apomorphine-induced emesis. 2) In the receptor binding assays, cephaeline and emetine had a distinct affinity to 5-HT4 receptor, but no or weak affinity to 5-HT1A, 5-HT3, nicotine, M3, beta1, NK1, and D2 receptors. 3) Cephaeline and emetine did not affect activities of metabolic enzymes of 5-HT and dopamine (MAO-A, MAO-B, tryptophan 5-hydroxylase and tyrosine hydroxylase) in vitro. These results suggest that 5-HT3 receptor plays an important role in the emetic action of TJN-119, cephaeline and emetine, and the 5-HT4 receptor may be involved in their mechanisms.
Research and Development Division, Tsumura & Co., Tokyo, Japan. hasegawa_masayuki@mail.tsumura.co.jp
Masayuki
M
Hasegawa
Toshinobu
T
Sasaki
Koichi
K
Sadakane
Masahiro
M
Tabuchi
Yasunori
Y
Takeda
Masayuki
M
Kimura
Yuichi
Y
Fujii
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004298:Dopamine / Q000378:metabolism; D004639:Emetics / Q000494:pharmacology*; D004640:Emetine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005289:Ferrets; D006168:Guinea Pigs; D006801:Humans; D007486:Ipecac / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D011485:Protein Binding; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology
D004639:Emetics; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D013469:Sulpiride; D007486:Ipecac; C005963:cephaelin; D004298:Dopamine; D004640:Emetine