Fukui H, Yamamoto M, Sasaki S, Sato S
Drug Safety Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Eur J Pharmacol. 1993 Dec 7;250(2):281-7. doi: 10.1016/0014-2999(93)90392-u.
The emetic effects of five anticancer drugs, cyclophosphamide, nitrogen mustard-N-oxide, actinomycin D, 5-fluorouracil and L-asparaginase, and the effects of bilateral abdominal vagotomy and bilateral greater splanchnic nerve section or a 5-HT3 receptor antagonist on the emesis induced by these drugs were investigated in dogs. Cyclophosphamide (20 mg/kg, i.v.), nitrogen mustard-N-oxide (5 mg/kg, i.v.) and actinomycin D (50 micrograms/kg, i.v.) caused vomiting in dogs with a long latency period. 5-Fluorouracil (5 mg/kg, i.v.) and L-asparaginase (2000 K.U./kg, i.v.) failed to induce vomiting. Bilateral abdominal vagotomy and bilateral greater splanchnic nerve section completely inhibited the vomiting induced by the former three anticancer drugs. Furthermore, the vomiting was inhibited completely by intravenous administration of ICS205930 (2 x 0.1 mg/kg), a 5-HT3 receptor antagonist. These results suggest that activation of visceral afferents through 5-HT3 receptors mediates the vomiting induced by cyclophosphamide, nitrogen mustard-N-oxide and actinomycin D.
研究了环磷酰胺、氮芥 - N - 氧化物、放线菌素D、5 - 氟尿嘧啶和L - 天冬酰胺酶这五种抗癌药物的催吐作用，以及双侧腹部迷走神经切断术、双侧内脏大神经切断术或5 - HT3受体拮抗剂对这些药物所致犬呕吐的影响。环磷酰胺（20mg/kg，静脉注射）、氮芥 - N - 氧化物（5mg/kg，静脉注射）和放线菌素D（50μg/kg，静脉注射）可使犬出现呕吐，但潜伏期较长。5 - 氟尿嘧啶（5mg/kg，静脉注射）和L - 天冬酰胺酶（2000K.U./kg，静脉注射）未能诱发呕吐。双侧腹部迷走神经切断术和双侧内脏大神经切断术完全抑制了前三种抗癌药物所致的呕吐。此外，静脉注射5 - HT3受体拮抗剂ICS205930（2×0.1mg/kg）可完全抑制呕吐。这些结果表明，通过5 - HT3受体激活内脏传入神经介导了环磷酰胺、氮芥 - N - 氧化物和放线菌素D所致的呕吐。
