Dyskinesias do not develop after chronic intermittent levodopa therapy in clinically hemiparkinsonian rhesus monkeys.
Dyskinesias do not develop after chronic intermittent levodopa therapy in clinically hemiparkinsonian rhesus monkeys.
复制标题
DOI：
10.1016/j.parkreldis.2010.10.010
复制
发表时间：
2011-01
影响因子：
4.1
通讯作者：
Subramanian T
中科院分区：
文献类型：
--
作者：
Lieu CA;Deogaonkar M;Bakay RA;Subramanian T
稳定的1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的帕金森病（PD）的偏侧帕金森（HP）恒河猴模型已被频繁用于测试临床前实验疗法，所述临床前实验疗法靶向治疗患有运动波动和药物诱导的运动障碍的晚期PD患者。我们回顾性分析了17只稳定的HP恒河猴的数据，这些猴长期接受慢性间歇性左旋多巴（LD）给药，试图诱导舞蹈徐动症样和张力障碍性运动障碍。用最佳剂量的LD治疗经多盲行为评定和18 F-多巴正电子发射断层扫描（PET）证实的HP稳定状态超过6个月的恒河猴，以提供单侧临床帕金森综合征的最大改善而没有任何副作用。此后，对每只动物进行慢性间歇性每日激发，LD剂量高达700 mg/天，经口或300 mg/kg/天胃肠外注射。尽管长期间歇性高剂量给药，LD治疗未能诱导这些动物出现舞蹈手足徐动症和肌张力障碍性运动障碍。这些结果表明，PD的稳定的严格单侧HP恒河猴模型可能不是测试针对运动障碍的实验疗法的合适动物模型，并且容易证明药物诱导的运动障碍和临床相关运动波动的双侧帕金森病恒河猴模型更适合用于治疗晚期PD患者的疗法的临床前实验测试。
The stable 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced hemiparkinsonian (HP) rhesus monkey model of Parkinson’s disease (PD) has been frequently used to test preclinical experimental therapeutics targeted to treat patients with advanced PD who suffer from motor fluctuations and drug-induced dyskinesias. We retrospectively analyzed data from 17 stable HP rhesus monkeys treated long-term with chronic intermittent dosing of levodopa (LD) in an attempt to induce choreoathetoid and dystonic dyskinesias. Rhesus monkeys in stable HP state for greater than 6 months as confirmed by multiple blinded behavioral ratings and 18F-dopa Positron Emission Tomography (PET) were treated with optimal doses of LD to provide maximal amelioration of unilateral clinical parkinsonism without any adverse effects. Thereafter, each animal was given chronic intermittent daily challenge with doses of LD up to 700 mg/day orally or with 300 mg/kg/day parenteral injections. LD treatments failed to induce choreoathetoid and dystonic dyskinesias in these animals despite chronic intermittent high dose administration. These results suggest that the stable strictly unilateral HP rhesus monkey model of PD may not be a suitable animal model to test experimental therapeutics targeted against dyskinesias, and that bilateral parkinsonian rhesus models that readily demonstrate drug-induced dyskinesias and clinically relevant motor fluctuations are more appropriate for preclinical experimental testing of therapies designed to treat patients with advanced PD.
登录
查看更多内容
影响因子：
3.3
作者：
FRANCOIS, C;PERCHERON, G;YELNIK, J
通讯作者：
YELNIK, J
影响因子：
5.3
作者：
Bankiewicz, KS;Daadi, M;Eberling, JL
通讯作者：
Eberling, JL
影响因子：
8.6
作者：
Kumar, N;Van Gerpen, JA;Ahlskog, JE
通讯作者：
Ahlskog, JE
DOI：
10.1007/bf01972287
发表时间：
1982-01-01
期刊：
EXPERIENTIA
影响因子：
--
作者：
COLLINGRIDGE, GL
通讯作者：
COLLINGRIDGE, GL
影响因子：
8.6
作者：
Ruzicka, E;Urgosík, D;Vladyka, V
通讯作者：
Vladyka, V