Kitani K, Kanai S, Carrillo M C, Ivy G O
Radioisotope Research Institute, Faculty of Medicine, University of Tokyo, Japan.
Ann N Y Acad Sci. 1994 Jun 30;717:60-71. doi: 10.1111/j.1749-6632.1994.tb12073.x.
(-)Deprenyl, a MAO-B inhibitor that is also known to be effective for symptoms of Parkinson's disease, when injected subcutaneously (sc) in male Fischer-344 rats at a dose of 0.5 mg/kg per day (3 times a week) from 18 months of age, significantly increased the remaining life expectancy. The average life span after 24 months was 34% greater in treated rats than in saline-treated control animals. Furthermore, a short-term (3 wk) continuous sc infusion of deprenyl significantly increased activities of superoxide dismutase and catalase but not of glutathione peroxidase in selective brain regions such as s. nigra, striatum, and cerebral cortex, but not in hippocampus or cerebellum, or the liver. The optimal dose for increasing these activities, however, differed greatly depending on the sex and age of animals, with a 10-fold lower value for young female than male rats. Interestingly, aging caused an increase and a decrease in the optimal dose in female and male rats, respectively. In addition, treatment for a longer term tended to reduce the optimal dosage in the same animal group. The results clearly demonstrate that deprenyl increases antioxidant enzyme activities in selective brain regions. If this effect of deprenyl is causally related to its life-prolonging effect, the dosage to be used for any life span study would be a critical factor, with the dosage differing widely depending on sex, age of animal, and mode and duration of drug administration.
（-）司来吉兰是一种单胺氧化酶B抑制剂，已知对帕金森病症状有效。从18月龄起，以每天0.5毫克/千克的剂量（每周3次）对雄性Fischer-344大鼠进行皮下注射，可显著延长其剩余预期寿命。24个月后，接受治疗的大鼠平均寿命比接受生理盐水治疗的对照动物长34%。此外，短期（3周）连续皮下输注司来吉兰可显著提高黑质、纹状体和大脑皮质等选择性脑区的超氧化物歧化酶和过氧化氢酶活性，但对海马、小脑或肝脏无此作用。然而，增加这些活性的最佳剂量因动物的性别和年龄差异很大，年轻雌性大鼠的最佳剂量比雄性大鼠低10倍。有趣的是，衰老分别导致雌性和雄性大鼠的最佳剂量增加和减少。此外，长期治疗往往会降低同一动物组的最佳剂量。结果清楚地表明，司来吉兰可提高选择性脑区的抗氧化酶活性。如果司来吉兰的这种作用与其延长寿命的作用存在因果关系，那么在任何寿命研究中使用的剂量将是一个关键因素，其剂量因动物的性别、年龄以及药物给药方式和持续时间而异。
