Vermeulen R J, Drukarch B, Sahadat M C, Goosen C, Wolters E C, Stoof J C
Graduate School Neurosciences Amsterdam, Vrije Universiteit, The Netherlands.
Mov Disord. 1994 Nov;9(6):664-72. doi: 10.1002/mds.870090613.
At present, the pharmacotherapy of Parkinson's disease (PD) consists mainly of L-dihydroxyphenylalanine (L-DOPA) and/or dopamine D2 receptor agonists. However, in general the clinical efficacy of D2 agonists is less than that of L-DOPA. Therefore, attention is being focussed on the role of the D1 receptor as a target for therapeutic intervention in PD. Recently, we reported that SKF 81297 is a selective D1 agonist that stimulates motor behavior of unilaterally MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-lesioned rhesus monkeys. Presently, we studied the effect of coadministration of SKF 81297 and the D2 agonist LY 171555 using the same model of PD. Coadministration of behaviorally active doses of SKF 81297 (0.3 mg/kg) and LY 171555 (0.01 mg/kg) resulted in a prolongation of the motor stimulation induced by either of the drugs alone. Neither administration of SKF 81297, in a dose of 0.03 mg/kg, nor of LY 171555, in a dose of 0.003 mg/kg, were behaviorally active, whereas the combined administration of these compounds induced a significant stimulation of motor behavior. These data suggest that (a) D1 receptor stimulation will prove to be useful in the treatment of PD and (b) better therapeutic results will be obtained by simultaneous stimulation of D1 and D2 receptors as compared with stimulation of both receptors alone.
目前，帕金森病（PD）的药物治疗主要包括左旋多巴（L-DOPA）和/或多巴胺D2受体激动剂。然而，总体而言，D2激动剂的临床疗效低于L-DOPA。因此，人们正将注意力集中在D1受体作为PD治疗干预靶点的作用上。最近，我们报道SKF 81297是一种选择性D1激动剂，可刺激单侧MPTP（1-甲基-4-苯基-1,2,3,6-四氢吡啶）损伤的恒河猴的运动行为。目前，我们使用相同的PD模型研究了SKF 81297和D2激动剂LY 171555联合给药的效果。行为活性剂量的SKF 81297（0.3 mg/kg）和LY 171555（0.01 mg/kg）联合给药导致单独使用任何一种药物诱导的运动刺激时间延长。0.03 mg/kg剂量的SKF 81297或0.003 mg/kg剂量的LY 171555单独给药均无行为活性，而这些化合物联合给药则显著刺激了运动行为。这些数据表明：（a）D1受体刺激在PD治疗中被证明是有用的；（b）与单独刺激D1和D2受体相比，同时刺激D1和D2受体将获得更好的治疗效果。
