Colpaert F C
Department of Psychopharmacology, Janssen Pharmaceutica, Beerse, Belgium.
Neuropharmacology. 1987 Sep;26(9):1431-40. doi: 10.1016/0028-3908(87)90110-9.
The experiments characterized the dose- and time-dependence of parkinsonian motor signs induced by reserpine in rats and a standardized system of manipulation of animals, evaluation of symptoms and analysis of data was devised. The assay procedure yielded no more than 0.5, 4.5 and 0.0% false positives with the evaluation of tremor, rigidity and hypokinesia, respectively. A dose-dependent and often complete blockade of all three signs was obtained with L-DOPA plus carbidopa (10:1) as well as with other classes of pharmacological agents that are used in the treatment of Parkinson's disease, i.e. direct or indirect dopamine (DA) agonists (amantadine, pergolide, lisuride) and inhibitors of monoamine oxidase (MAO) (clorgyline, pargyline, deprenyl, tranylcypromine). The inhibitor of the uptake of DA, nomifensine, and anticholinergics, 5-hydroxytryptamine (5-HT) antagonists, histamine antagonists and tricyclic antidepressants exerted little or no effect. The effects of putative agonists and antagonists at alpha 1- and alpha 2-adrenoceptors were also examined. Yohimbine blocked tremor and rigidity, but not hypokinesia, at 0.66 and 0.28 mg/kg, respectively. It is suggested that alpha-adrenergic mechanisms and, in particular, alpha 2-adrenoceptors, may be involved in reserpine-induced tremor and rigidity. Noradrenergic and dopaminergic systems can conceivably interact to progressively generate these different motor signs.
这些实验对利血平诱导大鼠帕金森运动体征的剂量和时间依赖性进行了表征，并设计了一个标准化的动物操作、症状评估和数据分析系统。在评估震颤、僵直和运动迟缓时，该检测程序分别产生不超过0.5%、4.5%和0.0%的假阳性结果。左旋多巴加卡比多巴（10:1）以及用于治疗帕金森病的其他几类药物，即直接或间接多巴胺（DA）激动剂（金刚烷胺、培高利特、利苏瑞）和单胺氧化酶（MAO）抑制剂（氯吉兰、帕吉林、司来吉兰、反苯环丙胺），均能产生剂量依赖性且常常能完全阻断所有这三种体征。多巴胺摄取抑制剂诺米芬辛、抗胆碱能药物、5-羟色胺（5-HT）拮抗剂、组胺拮抗剂和三环类抗抑郁药几乎没有作用或完全没有作用。还研究了α1和α2肾上腺素能受体的假定激动剂和拮抗剂的作用。育亨宾分别以0.66和0.28mg/kg的剂量阻断震颤和僵直，但不阻断运动迟缓。提示α-肾上腺素能机制，尤其是α2-肾上腺素能受体，可能参与利血平诱导的震颤和僵直。去甲肾上腺素能和多巴胺能系统可能相互作用，逐渐产生这些不同的运动体征。
