Dynorphin agonist therapy of Parkinson's disease.
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.
Giuffra
M
M
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892.
Mouradian
M M
MM
Davis
T L
TL
Ownby
J
J
Chase
T N
TN
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*
D011759:Pyrrolidines; D007980:Levodopa; D004399:Dynorphins; C051272:spiradoline