Mattocks A R, Driver E
Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, U.K.
Toxicol Lett. 1987 Oct;38(3):315-9. doi: 10.1016/0378-4274(87)90014-2.
Senaetnine is a new type of Senecio alkaloid with a dihydropyrrolizinone structure. A limited amount of the crude alkaloid was available for preliminary toxicity tests in weanling male rats via i.p., oral and i.v. routes. Single i.p. or p.o. doses up to 280 mg/kg were not acutely toxic, and showed no evidence of hepatotoxicity. The compound or its metabolites appeared to be eliminated rapidly via the kidneys. However, senaetnine had a direct irritant action on tissues near to the site of i.p. administration, and caused damage to pulmonary vascular tissue when given i.v. Senaetnine is closely related to, but less reactive than, dehydrosenecionine, a putative short-lived metabolite of the alkaloid senecionine. It possesses mild alkylating reactivity, and the evidence indicates that it can cause moderate tissue injury without the need for metabolic activation. This suggests the need for testing of this and related compounds for chronic toxicity and carcinogenicity.
赛乃宁是一种具有二氢吡咯里嗪酮结构的新型千里光生物碱。仅有少量粗生物碱可用于通过腹腔注射、口服和静脉注射途径对断奶雄性大鼠进行初步毒性试验。高达280mg/kg的单次腹腔注射或口服剂量无急性毒性，且无肝毒性证据。该化合物或其代谢产物似乎通过肾脏迅速消除。然而，赛乃宁对腹腔注射部位附近的组织有直接刺激作用，静脉注射时会对肺血管组织造成损伤。赛乃宁与脱氢千里光碱密切相关，但反应性低于脱氢千里光碱，脱氢千里光碱是生物碱千里光碱的一种假定的短寿命代谢产物。它具有轻度烷基化反应性，证据表明它可在无需代谢活化的情况下引起中度组织损伤。这表明需要对该化合物及相关化合物进行慢性毒性和致癌性测试。
