Wolff M C, Leander J D
Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, IN 46285, USA.
Eur J Pharmacol. 1997 Dec 11;340(2-3):217-20. doi: 10.1016/s0014-2999(97)01401-5.
LY228729 [(-)-4(dipropylamino)-1,3,4,5-tetrahydrobenz-[c,d]indole-6-carboxa mide]], an agonist at the 5-HT1A subtype of 5-HT receptor, was studied as an antiemetic in pigeons dosed with a highly emetic oncolytic agent, cyclophosphamide. An intramuscular injection of 0.32 mg/kg of LY228729 administered 15 min prior to the intravenous injection of 200 mg/kg of cyclophosphamide totally prevented the acute emetic response induced by cyclophosphamide. When used as a rescue therapy in a separate group of pigeons, LY228729 (0.32 mg/kg, i.m.) prevented further emetic episodes when it was administered after vomiting had already been induced by cyclophosphamide. Injections of LY228729 given at intervals over the next 2 d also attenuated the delayed emetic response induced by cyclophosphamide. LY228729 appears to be a broad spectrum antiemetic agent that is effective against the anticipatory, the acute and the delayed stages of emesis induced by oncolytic agents.
LY228729 [(-)-4-(二丙基氨基)-1,3,4,5-四氢苯并[c,d]吲哚-6-甲酰胺]，一种5-羟色胺（5-HT）受体5-HT1A亚型的激动剂，在给鸽子注射高致吐性溶瘤药物环磷酰胺时，被作为一种止吐药进行研究。在静脉注射200mg/kg环磷酰胺前15分钟，肌肉注射0.32mg/kg的LY228729可完全预防环磷酰胺诱导的急性呕吐反应。当在另一组鸽子中用作挽救疗法时，LY228729（0.32mg/kg，肌肉注射）在环磷酰胺已经诱发呕吐后给药，可预防进一步的呕吐发作。在接下来的2天里每隔一段时间注射LY228729，也可减轻环磷酰胺诱导的延迟性呕吐反应。LY228729似乎是一种广谱止吐药，对溶瘤药物诱导的呕吐的预期期、急性期和延迟期均有效。
