药用级特布他林在大鼠模型中无神经毒性。
Absence of neurotoxicity with medicinal grade terbutaline in the rat model.
机构信息
Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
出版信息
Reprod Toxicol. 2011 May;31(4):447-53. doi: 10.1016/j.reprotox.2011.01.001. Epub 2011 Jan 22.
To evaluate neurological effects of terbutaline, rats were injected with saline, terbutaline (Sigma or American Pharmaceutical Partners (APP™)) at 0.5 mg/kg-d or 10 mg/kg-d between postnatal days (PND) 2-5 or 11-14. Brains collected 24 h after last injection were used to determine corpus-callosum thickness, Purkinje cell and neuronal number in the cerebellum. Ambulation, distance traveled, resting time and time on rotarod were analyzed. Terbutaline (both doses/grades at PND 11-14) decreased corpus-callosum thickness. Ambulation time was significantly decreased in the 10 mg/kg-d (Sigma) and 0.5 mg/kg-d of terbutaline (APP™) (PND 2-5) juvenile-rats and 10 mg/kg-d-Sigma adult-rats, 0.5 mg/kg-d APP™ (PND 11-14) adult-rats. Resting time was increased in both doses of APP™ (PND 2-5) in juvenile-rats, 10 mg/kg-d Sigma adult-rats. 10 mg/kg-d-Sigma (PND 2-5) decreased distance traveled in adult-rats. 0.5 mg/kg-d-Sigma (PND 2-5 and PND 11-14) decreased the time spent on rotarod (30 RPM) in adult-rats. Sigma terbutaline Sigma had 2× as much free base compared to APP™. In conclusion, APP™ terbutaline did not have a deleterious effect on the developing rat brain.
为了评估特布他林的神经影响，在新生后第 2-5 天或第 11-14 天，给大鼠注射生理盐水、特布他林（Sigma 或美国制药伙伴公司（APP™））0.5mg/kg-d 或 10mg/kg-d。最后一次注射后 24 小时收集大脑，用于确定胼胝体厚度、小脑浦肯野细胞和神经元数量。分析了运动、行进距离、休息时间和旋转棒上的时间。特布他林（第 11-14 天的两个剂量/等级）降低了胼胝体厚度。0.5mg/kg-d APP（第 2-5 天的 Sigma）和 10mg/kg-d APP（第 11-14 天的 Sigma）的幼鼠以及 10mg/kg-d Sigma 的成年鼠的运动时间明显减少，0.5mg/kg-d APP（第 11-14 天的 APP）的成年鼠。在两种剂量的 APP（第 2-5 天的 Sigma）中，幼鼠的休息时间增加，10mg/kg-d Sigma 的成年鼠休息时间增加。10mg/kg-d Sigma（第 2-5 天）降低了成年鼠的行进距离。0.5mg/kg-d Sigma（第 2-5 天和第 11-14 天）降低了成年鼠在旋转棒（30RPM）上的时间。Sigma 特布他林 Sigma 的游离碱含量是 APP 的两倍。总之，APP 特布他林对发育中的大鼠大脑没有不良影响。
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