(S)-プラミペクソール二塩酸塩

説明Mirapex, an non ergot derivative, was launched in the US for treatment of Parkinson's disease. It can be prepared by two related routes, 5 steps and 3 steps, both involving an optical resolution with L-(+)-tartaric acid to afford the (S)-isomer. Mechanistically, it is a presynaptic dopamine D2 autoreceptor agonist which also activates D3-receptors. It is well absorbed from the GI and excreted in the urine essentially unchanged with a half-life of 8-12 hr. Mirapex had favorable effects on the symptoms without levodopa for patients with advanced PD and allowed a 27% reduction in use of levodopa in combination therapy. It had an adverse events profile similar to other dopamine agonists and in advanced patients reduced the mean "on-off" hr/day from 6 to 4. It was safe but not efficacious in all patients.

一般的な説明Pramipexole dihydrochloride,(S)-2-amino-6-propylamino-dihydrochloride(Mirapex), is a white to off-white powder soluble in water,slightly soluble in methanol and ethanol, and practically insolublein dichloromethane. Following oral administration,pramipexole is readily absorbed. Pharmacokinetic propertiesdiffer between men and women, with area under the curve(AUC) for each dose level being 35% to 43% greater inwomen, mainly because of a 24% to 27% lower oral clearance.The drug undergoes minimal hepatic biotransformationand is excreted virtually unchanged in the urine by the renaltubular secretion. Pramipexole interacts with drugs excretedby renal tubular secretion (H2-antagonists, diuretics, verapamil,quinidine, quinine), which leads to a decreased clearanceof pramipexole.44,45 Pramipexole is indicated fortreatment of the signs and symptoms of idiopathic PD, aloneor in combination with levodopa. It is also indicated for symptomatictreatment of moderate to severe idiopathic restlesslegs syndrome (RLS).