Fuller R W, Clemens J A, Hynes M D
J Clin Psychopharmacol. 1982 Dec;2(6):371-5.
Pergolide mesylate is a potent dopamine agonist that is being evaluated clinically in Parkinson disease, hyperprolactinemia, and other diseases. Pergolide activates both presynaptic and postsynaptic dopamine receptors, with some apparent selectivity for the presynaptic dopamine autoreceptors. In rats, low doses of pergolide (0.01 mg/kg or less, intraperitoneally) decreased dopamine turnover in brain, decreased serum prolactin concentration, and reduced blood pressure in spontaneously hypertensive rats. At somewhat higher doses (0.05 mg/kg or more, intraperitoneally), pergolide caused contralateral turning in nigrostriatal-lesioned rats, elevation of serum corticosterone, and hypermotility with stereotyped behavior. All of these actions are thought to be due to stimulation of dopamine receptors at various sites, but the data suggest that pergolide may have preferential affinity for presynaptic dopamine receptors. If low doses of pergolide can reduce dopaminergic transmission by activating presynaptic receptors that control dopamine release, then this action might be therapeutically useful in treating schizophrenia without causing tardive dyskinesia or in the treatment of tardive dyskinesia. The long duration of action of pergolide seen in animal and human studies could be an important advantage over some other dopamine agonists such as apomorphine.
甲磺酸培高利特是一种强效多巴胺激动剂，目前正在帕金森病、高泌乳素血症及其他疾病中进行临床评估。培高利特可激活突触前和突触后多巴胺受体，对突触前多巴胺自身受体具有一定的选择性。在大鼠中，低剂量的培高利特（0.01mg/kg或更低，腹腔注射）可降低脑内多巴胺周转率，降低血清泌乳素浓度，并降低自发性高血压大鼠的血压。在稍高剂量（0.05mg/kg或更高，腹腔注射）时，培高利特可导致黑质纹状体损伤大鼠出现对侧旋转、血清皮质酮升高以及伴有刻板行为的运动亢进。所有这些作用被认为是由于刺激了不同部位的多巴胺受体，但数据表明培高利特可能对突触前多巴胺受体具有优先亲和力。如果低剂量的培高利特可通过激活控制多巴胺释放的突触前受体来减少多巴胺能传递，那么这种作用在治疗精神分裂症而不引起迟发性运动障碍或治疗迟发性运动障碍方面可能具有治疗价值。在动物和人体研究中观察到的培高利特的长效作用可能是相对于其他一些多巴胺激动剂（如阿扑吗啡）的一个重要优势。
