Scheller Dieter, Dürmüller Nick, Moser Paul, Porsolt Roger D
Schwarz Biosciences, GmbH, Alfred-Nobel Strasse 10, Monheim, Germany.
Eur J Pharmacol. 2008 Apr 14;584(1):111-7. doi: 10.1016/j.ejphar.2008.01.038. Epub 2008 Feb 5.
Rotigotine is a new, non-ergoline dopamine receptor agonist developed for the treatment of Parkinson's disease in a transdermal formulation (Neupro ) to provide sustained drug delivery for 24 h with a once daily dosing. The aim of the present study was to determine whether or not continuous dopaminergic stimulation can interfere with the sleep-wake cycle. To achieve this, rotigotine was administered as a slow release formulation to provide stable plasma and brain levels over a period of 6 days and the sleep-wake cycle was evaluated in the freely-moving male rat using electroencephalagraphic recording. For comparison, the mixed dopamine/noradrenaline reuptake inhibitor nomifensine (16 mg/kg p.o.) was administered once daily for 6 days. In contrast to nomifensine, rotigotine (0.5 and 5 mg/kg s.c.) had no clear effects on the sleep-wake cycle. Nomifensine delayed the onset of rapid eye movement (REM) sleep and, to a lesser extent, also that of slow wave sleep (SWS). In addition, it increased the duration of waking time and decreased the duration of SWS and REM sleep. These effects were observed on all days and repeated administration lead neither to potentiation nor attenuation of the effects. It is concluded that a continuous dopaminergic stimulation of dopamine receptors by rotigotine may not only be beneficial for the treatment of the motor symptoms of Parkinson's disease but also have additional benefits by not compromising either sleep architecture or circadian rhythm.
罗替戈汀是一种新型非麦角林多巴胺受体激动剂，以透皮制剂（Neupro）形式开发用于治疗帕金森病，每日给药一次可实现24小时持续药物递送。本研究的目的是确定持续的多巴胺能刺激是否会干扰睡眠-觉醒周期。为实现这一目的，罗替戈汀以缓释制剂形式给药，在6天时间内维持稳定的血浆和脑内水平，并使用脑电图记录对自由活动的雄性大鼠的睡眠-觉醒周期进行评估。作为对照，混合多巴胺/去甲肾上腺素再摄取抑制剂诺米芬辛（16mg/kg口服）每日给药一次，持续6天。与诺米芬辛不同，罗替戈汀（0.5和5mg/kg皮下注射）对睡眠-觉醒周期没有明显影响。诺米芬辛延迟了快速眼动（REM）睡眠的开始，在较小程度上也延迟了慢波睡眠（SWS）的开始。此外，它增加了清醒时间的持续时间，减少了SWS和REM睡眠的持续时间。所有天数均观察到这些效应，重复给药既未导致效应增强也未导致效应减弱。得出的结论是，罗替戈汀对多巴胺受体的持续多巴胺能刺激不仅可能有益于帕金森病运动症状的治疗，而且通过不损害睡眠结构或昼夜节律还可能有额外益处。
