Schneider J S, Pope-Coleman A, Van Velson M, Menzaghi F, Lloyd G K
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Mov Disord. 1998 Jul;13(4):637-42. doi: 10.1002/mds.870130405.
The potential antiparkinsonian effects of the centrally acting, subtype-selective neuronal nicotinic acetylcholine receptor agonist (S)-(-)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)-pyridine (SIB-1508Y) was assessed on motor symptoms and disability scale ratings in three monkeys previously made parkinsonian by chronic exposure to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Compared with levodopa (L-dopa), SIB-1508Y exerted only mild antiparkinsonian effects when administered alone. Emetic effects of this drug interfered with potential therapeutic effects at higher doses. However, when a low, ineffective dose of SIB-1508Y was combined with low, ineffective doses of L-dopa, a significant clinical effect was observed. These data suggest that subtype-selective nicotinic acetylcholine receptor agonists may hold promise as antiparkinsonian agents, and when administered in combination with L-dopa may allow a reduction in the dose of L-dopa needed to achieve a significant clinical effect.
在三只先前因长期接触多巴胺能神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）而患帕金森病的猴子身上，评估了中枢作用的亚型选择性神经元烟碱型乙酰胆碱受体激动剂（S）-（-）-5-乙炔基-3-（1-甲基-2-吡咯烷基）吡啶（SIB-1508Y）对运动症状和残疾量表评分的潜在抗帕金森病作用。与左旋多巴（L-多巴）相比，单独给予SIB-1508Y时仅产生轻微的抗帕金森病作用。该药物的催吐作用在较高剂量时会干扰潜在的治疗效果。然而，当低剂量、无效剂量的SIB-1508Y与低剂量、无效剂量的L-多巴联合使用时，观察到了显著的临床效果。这些数据表明，亚型选择性烟碱型乙酰胆碱受体激动剂有望作为抗帕金森病药物，并且与L-多巴联合使用时，可能会减少达到显著临床效果所需的L-多巴剂量。
