Continuous delivery of rotigotine decreases extracellular dopamine suggesting continuous receptor stimulation.
Rotigotine, a non-ergolinic dopamine receptor agonist for treatment of Parkinson's disease was continuously administered over 48 h (0.5 mg/kg s.c., slow release formulation) to conscious rats striatally implanted with a microdialysis probe. Subsequently, the levels of rotigotine increased to a maximum of 3.42 + 2.1 nmol/l and remained at a level of 2.81 +/- 0.82 nmol/l for 48 h. Concomitantly, the dopamine levels consistently decreased to 20% of the control level. This suggests that the sustained administration of rotigotine provides stable extracellular drug levels in the striatum resulting in continuous stimulation of dopamine receptors.
Kehr
J
J
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Hu
X-J
XJ
Goiny
M
M
Scheller
D K A
DK
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D008297:Male; D017551:Microdialysis; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D013997:Time Factors
D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine; D004298:Dopamine