Todd G C, Griffing W J, Gibson W R, Morton D M
Cancer Treat Rep. 1979 Jan;63(1):35-41.
Neurotoxicity is the major side effect occurring during the clinical use of vincristine (VCR). Animal models predictive of potential neurotoxicity would be very useful in the preclinical development of new vinca compounds. To simulate conditions in which neurotoxicity is produced during the clinical use of VCR, experimental animals (except the guinea pig) were given the test compounds by the iv route over a prolonged time period. Doses were selected based on the production of leukopenia. Vindesine (VDS), a chemically modified vinblastine (VBL) product, was compared with VCR and VBL in animal studies. Definite neurotoxic manifestations developed when VCR was given to chickens, cats, and monkeys. The administration of VDS or VBL did not produce neurotoxic signs in these species. The mouse, rat, dog, and guinea pig were not found to be useful models. Thus, it would appear the chicken, cat, and monkey would be appropriate animal models for the preclinical testing of new vinca compounds.
神经毒性是长春新碱（VCR）临床使用过程中出现的主要副作用。能够预测潜在神经毒性的动物模型对于新型长春花属化合物的临床前开发非常有用。为了模拟VCR临床使用过程中产生神经毒性的情况，实验动物（豚鼠除外）在较长时间段内通过静脉途径给予受试化合物。根据白细胞减少的情况选择剂量。在动物研究中，将化学修饰的长春碱（VBL）产物长春地辛（VDS）与VCR和VBL进行了比较。给鸡、猫和猴子注射VCR时出现了明确的神经毒性表现。在这些物种中，给予VDS或VBL未产生神经毒性迹象。未发现小鼠、大鼠、狗和豚鼠是有用的模型。因此，鸡、猫和猴子似乎是新型长春花属化合物临床前测试的合适动物模型。
