Continuous stimulation of dopaminergic receptors by rotigotine does not interfere with the sleep-wake cycle in the rat.
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.
Scheller
Dieter
D
Schwarz Biosciences, GmbH, Alfred-Nobel Strasse 10, Monheim, Germany. dieter.scheller@schwarzpharma.com
Dürmüller
Nick
N
Moser
Paul
P
Porsolt
Roger D
RD
D000284:Administration, Oral; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects*; D003692:Delayed-Action Preparations; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004569:Electroencephalography; D007279:Injections, Subcutaneous; D008297:Male; D009627:Nomifensine / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology*; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*; D014851:Wakefulness / Q000187:drug effects*
D018759:Adrenergic Uptake Inhibitors; D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D009627:Nomifensine; C047508:rotigotine