Eden R J, Costall B, Domeney A M, Gerrard P A, Harvey C A, Kelly M E, Naylor R J, Owen D A, Wright A
SmithKline Beecham Research, Welwyn, Herts, England.
Pharmacol Biochem Behav. 1991 Jan;38(1):147-54. doi: 10.1016/0091-3057(91)90603-y.
These studies characterise the pharmacology of ropinirole, a selective D-2 agonist. High-affinity human caudate binding revealed a Ki for D2 receptors of 2.9 x 10(-8) M with no affinity for D1 at 10(-4) M in the rat. Ropinirole was weakly active at alpha 2-adrenoceptors and 5-HT2 receptors but inactive at 5-HT1, benzodiazepine and gamma-aminobutyric acid receptors or alpha 1 and beta-adrenoceptors. In rodents, ropinirole, like apomorphine, caused biphasic spontaneous locomotor activity and contralateral circling in 6-OHDA-lesioned mice with no tolerance to the latter after 14 days treatment. Amphetamine caused ipsilateral responses in the lesioned mice. Ropinirole did not cause marked stereotypies. In marmosets ropinirole (0.05-1.0 mg/kg SC or 0.1 mg/kg PO) reversed all motor and behavioural deficits induced by MPTP. This response started 10-20 minutes after dosing, and exceeded 2 hours. No tolerance was seen following chronic b.i.d. treatment. Similar results were obtained with 1-dopa plus benserazide; however, 1-dopa always caused emesis, whereas beneficial effects were shown with ropinirole in the absence of this side effect. These results support the continued clinical assessment of ropinirole for the treatment of Parkinson's disease.
这些研究对罗匹尼罗（一种选择性D-2激动剂）的药理学特性进行了描述。高亲和力的人体尾状核结合实验显示，罗匹尼罗对D2受体的Ki值为2.9×10⁻⁸ M，在大鼠体内，10⁻⁴ M浓度下对D1受体无亲和力。罗匹尼罗对α2-肾上腺素能受体和5-HT2受体有微弱活性，但对5-HT1、苯二氮䓬和γ-氨基丁酸受体或α1和β-肾上腺素能受体无活性。在啮齿动物中，罗匹尼罗与阿扑吗啡一样，在6-OHDA损伤的小鼠中引起双相性自发运动活动和对侧旋转，治疗14天后对后者无耐受性。苯丙胺在损伤小鼠中引起同侧反应。罗匹尼罗不会引起明显的刻板行为。在狨猴中，罗匹尼罗（0.05 - 1.0 mg/kg皮下注射或0.1 mg/kg口服）可逆转MPTP诱导的所有运动和行为缺陷。这种反应在给药后10 - 20分钟开始，持续超过2小时。每日两次慢性给药后未见耐受性。左旋多巴加苄丝肼也得到了类似结果；然而，左旋多巴总是引起呕吐，而罗匹尼罗在无此副作用的情况下显示出有益效果。这些结果支持对罗匹尼罗治疗帕金森病进行持续的临床评估。
