Hasegawa Masayuki, Sasaki Toshinobu, Sadakane Koichi, Tabuchi Masahiro, Takeda Yasunori, Kimura Masayuki, Fujii Yuichi
Research and Development Division, Tsumura & Co., Tokyo, Japan.
Jpn J Pharmacol. 2002 Jun;89(2):113-9. doi: 10.1254/jjp.89.113.
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.
由药用吐根制备的吐根糖浆含有催吐生物碱吐根酚碱和吐根碱。研究了受体以及5-羟色胺和多巴胺代谢酶在吐根糖浆及其成分所致呕吐中的作用。1）在雪貂中，选择性5-HT3受体拮抗剂昂丹司琼（0.5mg/kg，口服）可预防TJN-119（0.5mL/kg，口服）、吐根酚碱（0.5mg/kg，口服）和吐根碱（5.0mg/kg，口服）所致的每次呕吐，但腹腔注射选择性多巴胺D2受体拮抗剂舒必利，在剂量为0.1mg/kg时虽能阻断阿扑吗啡所致呕吐，却未能显著抑制TJN-119、吐根酚碱和吐根碱所致呕吐。2）在受体结合试验中，吐根酚碱和吐根碱对5-HT4受体有明显亲和力，但对5-HT1A、5-HT3、烟碱、M3、β1、NK1和D2受体无亲和力或只有微弱亲和力。3）吐根酚碱和吐根碱在体外不影响5-羟色胺和多巴胺代谢酶（MAO-A、MAO-B、色氨酸5-羟化酶和酪氨酸羟化酶）的活性。这些结果表明，5-HT3受体在TJN-119、吐根酚碱和吐根碱的催吐作用中起重要作用，5-HT4受体可能参与其作用机制。
