神经功能观察组合法评价神经系统药物对幼龄Beagle 犬的影响
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1.广州医药研究总院有限公司药物非临床评价研究中心,广州 510240;2.广州医药研究总院有限公司国家犬类实验动物资源库,广州 510240

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R-332;R994. 1;R965. 3

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Effects of neurological drugs on juvenile Beagle dogs assessed using the functional observation battery method
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1. Center for Drug Non-clinical Evaluation and Research of Guangzhou General Pharmaceutical Research Institute,Guangzhou 510240, China. 2. National Canine Laboratory Animal Resources of Guangzhou General Pharmaceutical Research Institute, Guangzhou 510240

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    摘要:

    目的 采用神经功能观察组合(FOB)法,评价不同神经系统药物对幼龄 Beagle 犬的影响,为儿科神经系统用药的研究提供合适的评价方法和准确的数据支持。 方法 将幼龄 Beagle 犬随机设计为阴性对照组、尼可刹米组(25 mg / kg)、咖啡因组(30 mg / kg)和苯巴比妥组(12 mg / kg)。 所有组别均采用单次给药,阴性对照组给予 0. 9%氯化钠注射液,其余组给予相应药物。 在给药前、给药后 1、2、3 h 时间点对实验动物各进行 1 次 FOB。 结果 药物干预后,与阴性对照组相比,尼可刹米组动物呼吸加快、对面部感觉刺激的反应增加(P<0. 05),1 / 6 动物出现呕吐;咖啡因组动物呼吸加快、视觉/ 听觉刺激反应升高、本体感受定位响应加快(P<0. 05),1 / 6 动物舌下神经反射异常、3 / 6 动物出现刻板行为(P<0. 05);苯巴比妥组动物颈部肌张力、肢体肌张力均下降、本体感受定位响应变慢(P<0. 05),伸肌蹬踏反应、肱三头肌反射、髌骨反射均降低( P<0. 05)。 结论 在本实验条件下,本研究建立的 FOB 法是评价幼龄 Beagle 犬神经系统类儿科药物毒性的一种较好的方法,可有效评价临床常用神经系统药物如尼可刹米、咖啡因、苯巴比妥引起的特定毒性表现。

    Abstract:

    Objective To provide appropriate evaluation method and accurate data to support the study of pediatric nervous system drugs, the functional observation battery (FOB) was used to evaluate the effects of different nervous system drugs on juvenile Beagle dogs. Methods Juvenile Beagles were randomly assigned to negative control, nikethamide ( 25 mg / kg), caffeine ( 30 mg / kg), and phenobarbital groups ( 12 mg / kg). All groups received a single administration; the negative control group was administered 0. 9% sodium chloride by injection,while the other groups received their respective drugs. FOB assessments were conducted at baseline (pre-dose) and 1, 2, and 3 h post-dose. Results Compared with the negative control group, the nikethamide group exhibited increased respiratory rate and enhanced facial sensory examination scores following drug intervention (P<0. 05), with vomiting observed in 1 / 6 animals. The caffeine group showed increased respiratory rate, elevated responses to visual and auditory stimuli, and accelerated proprioceptive positioning (P<0. 05), along with abnormal hypoglossal reflex in1 / 6 animals and stereotyped behavior in 3 / 6 ( P<0. 05). The phenobarbital group demonstrated decreased neck muscle and limb tone as well as slowed proprioceptive positioning (P<0. 05), with reduced extensor postural thrust,triceps, and patellar reflexes (P<0. 05). Conclusions In this study, the FOB method appears to be suitable for evaluating pediatric nervous system drug toxicity in juvenile Beagles. It effectively identified specific toxic manifestations induced by commonly used clinical nervous system drugs, such as nikethamide, caffeine, and phenobarbital.

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陈健钊,陈洁君,李日许,胡敏华,张超恒,谭秋怡,郭秋平.神经功能观察组合法评价神经系统药物对幼龄Beagle 犬的影响[J].中国比较医学杂志,2026,36(15):73~82.

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  • 收稿日期:2025-07-22
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  • 在线发布日期: 2026-09-01
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