While levodopa is still considered the cornerstone of treatment of Parkinson’s
disease, many patients begin to experience treatment-related problems, such as a
wearing-off phenomenon and the development of dyskinesias as the disease
progresses. Continuous dopaminergic stimulation by means of a dopamine
agonist has been recognized as being associated with a lower incidence of
dyskinesias. Using a selective dopamine agonist as monotherapy in early disease
may delay the onset of levodopa therapy, or at a minimum, lower its dose in
adjunctive situations to minimize the adverse neurotoxic effects of levodopa.
Rotigotine is a nonergolinic dopamine D3/D2/D1 receptor agonist, and it is the
first dopamine agonist to be launched as a transdermal patch.
용도
It is a non-ergot dopamine agonist drug and is indicated for the treatment of Parkinson disease.
일반 설명
Rotigotine, (6S)-6-{propyl[2-(2-thienyl)ethyl]amino}-5,6,7,8-tetrahydro-1-naphthalenol (Neupro),is a nonergoline that is available as a silicone-based, selfadhesivematrix, transdermal system for continuous delivery over a 24-hour period. Approximately 45% of the drug is releasedwithin 24 hours. The terminal half-life of rotigotine is5 to 7 hours after removal of the patch. Rotigotine is 90%bound to plasma proteins. The compound undergoes extensivemetabolism and has low bioavailability by the oralroute. The major metabolites of rotigotine are the glucuronideand sulfate conjugates of rotigotine and sulfateconjugates of N-despropylrotigotine and N-desthienylethylrotigotine. Rotigotine is excreted in the urine (71%) andfeces (11%).Studies using human liver microsomes didnot find any interactions with CYP1A2, CYP2C9,CYP2C19, CYP2D6, and CYP3A4 substrates.Rotigotinetransdermal system contains sodium metabisulfite, and individualssensitive to sulfite could be at risk for allergic reactions.Additionally, somnolence is a common adverse reactionwith individuals on rotigotine, and patients should beclosely monitored during therapy.In transfected Chinesehamster ovary (CHO) cells, rotigotine binds with high affinityat D3 and D2L receptors (variants in the D2 receptor subtypeare caused by insertion of the 29 amino acids into thethird loop to give D2s and D2L).Using rat CHO cells,rotigotine shows over 30-fold selectivity at D3 versus D2 receptors.48 Rotigotine was approved in May 2007 for thetreatment of early-stage PD.
