title: Dynorphin agonist therapy of Parkinson's disease.
abstract: Striatal dynorphin system function may be altered in Parkinson's disease. To evaluate whether treatment with a selective dynorphin agonist improves motor symptoms, four parkinsonian patients received single daily injections of spiradoline under controlled conditions. Doses ranging from 1 to 4 micrograms/kg had no discernible effect on motor performance when given alone or in combination with levodopa-carbidopa. Three patients developed dose-limiting adverse effects, especially behavioral alterations. These results suggest that dynorphin replacement strategies, using spiradoline-like kappa-1 agonists, may have limited value in the therapy of patients with Parkinson's disease.
authors.affiliation: Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892.
authors.forename: M
authors.initials: M
authors.lastname: Giuffra
authors.forename: M M
authors.initials: MM
authors.lastname: Mouradian
authors.forename: T L
authors.initials: TL
authors.lastname: Davis
authors.forename: J
authors.initials: J
authors.lastname: Ownby
authors.forename: T N
authors.initials: TN
authors.lastname: Chase
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004399:Dynorphins / Q000502:physiology*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D011759:Pyrrolidines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D011759:Pyrrolidines; D007980:Levodopa; D004399:Dynorphins; C051272:spiradoline