L-Dopa methyl ester--a candidate for chronic systemic delivery of L-Dopa in Parkinson's disease.
Continuous intravenous infusions of L-Dopa as a treatment for response swings in Parkinson's disease are limited by the insolubility and acidity of L-Dopa. Its methyl ester is a soluble neutral derivative that might be of benefit to these patients, and is examined in the present study in behavioural and biochemical animal models. On intraperitoneal or subcutaneous administration to mice L-Dopa methyl ester was equivalent to L-Dopa in reversing reserpine-induced akinesia and producing contraversive circling behaviour in rats with a 6-hydroxydopamine lesion of the medial forebrain bundle. On oral administration the methyl ester was more active. The administration of L-Dopa or the methyl ester produced equivalent changes in striatal and mesolimbic dopamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid metabolite levels. We suggest that systemic or subcutaneous infusion of L-Dopa methyl ester to patients who experience response fluctuations may provide a means of maintaining mobility.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D000978:Antiparkinson Agents; D003342:Corpus Striatum / Q000032:analysis; D004195:Disease Models, Animal; D007980:Levodopa / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008032:Limbic System / Q000032:analysis; D008297:Male; D051379:Mice; D010300:Parkinson Disease / Q000188:drug therapy*; D012110:Reserpine / Q000037:antagonists & inhibitors
D000978:Antiparkinson Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D012110:Reserpine; C035420:levodopa methyl ester